Pharmaceutical compositions of albumin and rapamycin

Abstract

Compositions comprising nanoparticles comprising albumin and rapamycin, and commercial batches of such compositions are provided.SOLUTION: A nanoparticle composition comprising (a) nanoparticles comprising rapamycin and albumin and (b) a non-nanoparticle portion comprising albumin and rapamycin, wherein about 80% to about 95% of the albumin in the composition is in the form of monomeric albumin and about 4% to about 15% of the albumin in the composition is in the form of dimeric albumin, as measured by subjecting the composition to size exclusion chromatography (SEC) with a saline mobile phase coupled with a multi-angle light scattering (MALS) detector, wherein the percentage of albumin in the composition that is in the form of monomeric albumin, dimeric albumin or polymeric albumin is determined by: And wherein about 0.5% to about 5% of the albumin in the composition is in the form of polymeric albumin.SELECTED DRAWING: Figure 11

Description

[Technical Field]

[0001] (Cross-reference to related occurrence) This application claims priority to U.S. Provisional Patent Application No. 62 / 927,047, filed October 28, 2019; and U.S. Provisional Patent Application No. 62 / 936,212, filed November 15, 2019, each of which is incorporated herein by reference for all purposes.

[0002] (Technical field of the invention) Described herein are compositions containing nanoparticles with albumin and rapamycin, and emulsions containing albumin and rapamycin. Additionally, methods for preparing and / or controlling the quality of such compositions and emulsions are described. [Background technology]

[0003] The mammalian target of rapamycin (mTOR) is a conserved serine / threonine kinase that integrates intracellular and extracellular signals and serves as a central hub for intracellular signaling to regulate cell growth and homeostasis. Activation of the mTOR pathway is associated with cell proliferation and survival, while inhibition of mTOR signaling leads to inflammation and cell death. Dysregulation of the mTOR signaling pathway has been implicated in the rise of several human diseases, including cancer and autoimmune disorders. Consequently, mTOR inhibitors have found widespread application in the treatment of diverse pathological conditions, such as solid tumors, hematological malignancies, organ transplants, restenosis, and rheumatoid arthritis.

[0004] Rapamycin, also known as sirolimus (INN / USAN), is an immunosuppressant used to prevent rejection in organ transplants; it is particularly useful in kidney transplants. Rapamycin-eluting stents have been approved in the United States for treating coronary artery restenosis. Furthermore, rapamycin has been demonstrated as an effective inhibitor of tumor growth in various cell lines and animal models. Other limus drugs, such as rapamycin analogs, have been designed to improve the pharmacokinetic and pharmacodynamic properties of rapamycin. For example, temsirolimus has been approved in the United States and Europe for the treatment of renal cell carcinoma. Everolimus has been approved in the United States for the treatment of advanced breast cancer, pancreatic neuroendocrine tumors, advanced renal cell carcinoma, and subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex. Rapamycin's mode of action is to bind to the cytosolic protein FK-binding protein 12 (FKBP12), and this rapamycin-FKBP12 complex then inhibits the mTOR pathway by directly binding to mTOR complex 1 (mTORC1).

[0005] Albumin-based nanoparticle compositions have been developed as a drug delivery system for delivering substantially water-insoluble drugs.See, for example, U.S. Patent Nos. 5,916,596, 6,506,405, 6,749,868, 6,537,579, 7,820,788 and 7,923,536.Nabic-paclitaxel, which is an albumin-stabilized nanoparticle formulation of paclitaxel and is sold under the trade name ABRAXANE®, has been approved in the United States and various other countries for treating metastatic breast cancer, pancreatic cancer and lung cancer. The disclosures of all publications, patents, patent applications and published patent applications mentioned herein are hereby incorporated by reference in their entirety. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 5,916,596 [Patent Document 2] U.S. Patent No. 6,506,405 [Patent Document 3] U.S. Patent No. 6,749,868 [Patent Document 4] U.S. Patent No. 6,537,579 [Patent Document 5] U.S. Patent No. 7,820,788 [Patent Document 6] U.S. Patent No. 7,923,536 Summary of the Invention

[0007] Nanoparticle compositions, pharmaceutical compositions, and emulsions containing rapamycin and albumin are described herein, along with commercial batches of such nanoparticle compositions, pharmaceutical compositions, and emulsions. Methods for preparing such nanoparticle compositions, pharmaceutical compositions, and emulsions, as well as methods for using such nanoparticle compositions, pharmaceutical compositions (including, for example, those for treating cancer), and emulsions are also described. Additionally, methods for evaluating the suitability of pharmaceutical compositions for use in human individuals, and methods for processing pharmaceutical compositions (and commercial batches of such pharmaceutical compositions) identified as suitable for use in human individuals are described herein.

[0008] Nanoparticle composition parameters, such as those described herein, can be used to ensure consistency during the manufacture of the composition. The nanoparticles contain rapamycin, a drug known to be effective in cancer treatment, and predictable release of the drug is important for reliable treatment. Consistently manufactured nanoparticles are expected to have a consistent drug release profile. Changes in manufacturing protocols, such as scale-up during commercial batch manufacturing, can result in changes in the physical and functional parameters of the nanoparticle composition. Described herein are commercial batches of nanoparticle compositions and commercial batches of emulsions used to manufacture commercial batches of nanoparticle compositions, with physical and functional parameters determined for the commercial batches.

[0009] Nanoparticle compositions described herein can include (a) nanoparticles comprising rapamycin and albumin, and (b) non-nanoparticle portions comprising albumin and rapamycin. In some embodiments, the nanoparticles comprise a core comprising rapamycin and a coating comprising albumin.

[0010] In a nanoparticle composition, or a commercial batch of such a nanoparticle composition, the percentage of albumin in the composition that is in the form of monomeric, dimeric, or polymeric albumin is determined by subjecting the composition to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector, and the percentage of albumin in the composition that is in the form of monomeric albumin is about 80% to about 95% of the albumin in the composition is in the form of monomeric albumin, about 4% to about 15% of the albumin in the composition is in the form of dimeric albumin, and about 0.5% to about 5% of the albumin in the composition is in the form of polymeric albumin. The proportion of albumin in the nanoparticle portion of the composition that is in the form of monomeric albumin, dimeric albumin, or polymeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion, resuspending the nanoparticles in saline, and subjecting the resuspended nanoparticles to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector. The proportion of albumin in the nanoparticle portion that is in the form of monomeric albumin is about 70% to about 85% of the albumin in the nanoparticle portion, about 9% to about 20% of the albumin in the nanoparticle portion is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticle portion is in the form of polymeric albumin. The proportion of albumin in the non-nanoparticle portion of the composition that is in the form of monomeric, dimeric, or polymeric albumin is determined by separating the nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector, and the proportion of albumin in the non-nanoparticle portion is about 80% to about 95% in the form of monomeric albumin, about 4% to about 14% in the form of dimeric albumin, and about 0.5% to about 5% in the form of polymeric albumin. The nanoparticle composition may be further characterized in that less than 3% by weight of the combined seco-rapamycin and rapamycin in the composition is in the form of seco-rapamycin.

[0011] In another characterization of a nanoparticle composition or a commercial batch of a nanoparticle composition, the proportion of albumin in the nanoparticle portion that is in the form of polymeric albumin other than oligomeric albumin is determined by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, and found that about 42% to about 60% of the albumin in the nanoparticle portion is in the form of polymeric albumin other than oligomeric albumin. The proportion of albumin in the nanoparticle portion that is in the form of oligomeric albumin is determined by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, and found that about 1% to about 4.5% of the albumin in the nanoparticle portion is in the form of oligomeric albumin. The proportion of albumin in the nanoparticle portion that is in the form of monomeric or dimeric albumin is determined by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, resulting in about 25% to about 50% of the albumin in the nanoparticle portion being in the form of monomeric albumin, or about 5% to about 16% of the albumin in the nanoparticle portion being in the form of dimeric albumin. For the non-nanoparticle portion, the proportion of albumin in the non-nanoparticle portion that is in the form of monomeric albumin, dimeric albumin, oligomeric albumin, and / or polymeric albumin other than oligomeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography. The proportion of albumin in the non-nanoparticle portion is about 80% to about 95% in the form of monomeric albumin, about 4% to about 14% in the form of dimeric albumin, about 0.5% to about 4% in the form of oligomeric albumin, and / or about 0.5% to about 3% in the form of polymeric albumin other than oligomeric albumin.The composition as a whole may be characterized in that, when the proportion of monomeric albumin, dimeric albumin, oligomeric albumin, and / or polymeric albumin other than oligomeric albumin in the composition is determined by subjecting the composition to size exclusion chromatography, about 80% to about 95% of the total albumin in the composition is in the form of monomeric albumin, about 4% to about 15% of the total albumin in the composition is in the form of dimeric albumin, about 0.3% to about 3% of the total albumin in the composition is in the form of oligomeric albumin, and / or about 2% to about 7% of the total albumin in the composition is in the form of polymeric albumin other than oligomeric albumin. The nanoparticle composition may be further characterized in that less than 3% by weight of the total of seco-rapamycin and rapamycin in the composition is in the form of seco-rapamycin.

[0012] In some embodiments of the nanoparticle composition, about 70% to about 85% of the albumin in the nanoparticle portion is in the form of monomeric albumin. In some embodiments, about 5% to about 15% of the albumin in the nanoparticle portion is in the form of polymeric albumin. In some embodiments, about 9% to about 20% of the albumin in the nanoparticle portion is in the form of dimeric albumin. In some embodiments, about 0.5% to about 5% of the albumin in the non-nanoparticle portion is in the form of polymeric albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion is in the form of monomeric albumin. In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion is in the form of dimeric albumin. In some embodiments, about 0.5% to about 5% of the total albumin in the composition is in the form of polymeric albumin. In some embodiments, about 80% to about 95% of the total albumin in the composition is in the form of monomeric albumin. In some embodiments, about 4% to about 15% of the total albumin in the composition is in the form of dimeric albumin. In some embodiments, the percentage of polymeric, dimeric, or monomeric albumin is measured using size exclusion chromatography.

[0013] In some embodiments of the nanoparticle composition, the nanoparticles have a volume-weighted mean particle size of about 200 nm or less. In some embodiments, the nanoparticles have a volume-weighted mean particle size of about 50 nm to about 200 nm. In some embodiments, the nanoparticles have a Z-average particle size of about 200 nm or less. In some embodiments, the nanoparticles have a Z-average particle size of about 50 nm to about 200 nm.

[0014] In some embodiments of the nanoparticle composition, the nanoparticles have a polydispersity index of less than 0.2. In some embodiments, the nanoparticles have a polydispersity index of about 0.03 to about 0.2. In some embodiments, the nanoparticles have a particle size distribution range (D v 95-D v 5) / D v 50) is about 0.8 to about 1.2.

[0015] In some embodiments of the nanoparticle composition, the weight percent of albumin in the nanoparticle portion is about 25% to about 45%. In some embodiments, the weight percent of rapamycin in the nanoparticle portion is about 55% to about 75%. In some embodiments, the weight ratio of albumin to rapamycin in the nanoparticle portion is about 1:1 to about 1:4.

[0016] In some embodiments of the nanoparticle composition, the weight ratio of albumin to rapamycin in the composition is from about 1:1 to about 10:1.

[0017] In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion, hi some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles.

[0018] In some embodiments of the nanoparticle composition, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition, such as a powder. In some embodiments, the nanoparticles have been resuspended from a dry composition.

[0019] In some embodiments of the nanoparticle composition, the concentration of albumin in the composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the concentration of albumin in the composition in the non-nanoparticle portion is about 30 mg / mL to about 100 mg / mL. In some embodiments, the concentration of albumin in the nanoparticle composition in the nanoparticle portion is about 1 mg / mL to about 5 mg / mL. In some embodiments, the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL. In some embodiments, the concentration of rapamycin in the composition in the non-nanoparticle portion is about 20 μg / mL to about 55 μg / mL. In some embodiments, the concentration of rapamycin in the composition in the nanoparticle portion is about 1 mg / mL to about 15 mg / mL.

[0020] In some embodiments of the nanoparticle composition, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5.

[0021] In some embodiments of the nanoparticle composition, the composition is stable for at least 24 hours at 25° C. In some embodiments, the composition is stable for at least 24 hours at 4° C.

[0022] In some embodiments of the nanoparticle composition, the composition comprises less than 10 μg / mL of tert-butanol. In some embodiments, the composition comprises tert-butanol. In some embodiments, the composition comprises less than 5 μg / mL of chloroform. In some embodiments, the composition comprises chloroform.

[0023] In some embodiments of the nanoparticle composition, the nanoparticles have a zeta potential of about -25 mV to about -50 mV.

[0024] In some embodiments of the nanoparticle composition, the composition has an amorphous morphology as determined by measuring the crystallinity of a lyophilized form of the composition by X-ray diffraction. In some embodiments, the nanoparticles have an amorphous morphology as determined by isolating the nanoparticles from the composition, lyophilizing the isolated nanoparticles, and measuring the crystallinity of the isolated and lyophilized nanoparticles by X-ray diffraction.

[0025] In some embodiments of the nanoparticle composition, the rapamycin in the nanoparticles has an amorphous morphology as determined by Raman spectroscopy, polarized light microscopy, differential scanning calorimetry (DSC), modulated differential scanning calorimetry (mDSC), Fourier transform infrared (FTIR) spectroscopy, or nuclear magnetic resonance (NMR) spectroscopy.

[0026] In some embodiments of the nanoparticle composition, the vinyl chains of the rapamycin in the nanoparticle portion interact with albumin in the nanoparticle.

[0027] In some embodiments of the nanoparticle composition, at least a portion of the nanoparticles are non-spherical, hi some embodiments, at least 20% of the nanoparticles in the composition are non-spherical.

[0028] In some embodiments of the nanoparticle composition, the nanoparticle composition comprises less than about 3% by weight of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin in the nanoparticles, hi some embodiments, the nanoparticle composition comprises more than about 0.2% by weight of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin in the nanoparticles.

[0029] In some embodiments of the nanoparticle composition, no more than about 3% of the rapamycin in the nanoparticle composition is free rapamycin.

[0030] In some embodiments of the nanoparticle composition, the albumin is human albumin.

[0031] In some embodiments of the nanoparticle composition, the nanoparticle composition is sterile.

[0032] In some embodiments of the nanoparticle composition, the nanoparticle composition is sterilized by filtration.

[0033] In some embodiments of the nanoparticle composition, the nanoparticle composition is contained within a sealed container. In some embodiments, the sealed container is a sealed vial or a sealed bag.

[0034] In some embodiments of the nanoparticle composition, the nanoparticle composition is a pharmaceutical composition.

[0035] Also described herein are emulsions (e.g., commercial batch emulsions) comprising a dispersed organic phase comprising nanodroplets comprising rapamycin dissolved in an organic solvent comprising chloroform and tert-butanol, and a continuous aqueous phase comprising albumin.

[0036] In some embodiments of the emulsion, the organic solvent comprises about 10% to about 50% by volume of tert-butanol. In some embodiments, the organic solvent comprises about 50% to about 90% by volume of chloroform. In some embodiments, the organic solvent comprises a volume ratio of chloroform and tert-butanol of about 1:1 to about 9:1.

[0037] In some embodiments of the emulsion, the concentration of rapamycin in the organic phase is from about 20 mg / mL to about 500 mg / mL. In some embodiments, the concentration of rapamycin in the emulsion is from about 2 mg / mL to about 50 mg / mL. In some embodiments, the concentration of albumin in the aqueous phase is from about 10 mg / mL to about 200 mg / mL. In some embodiments, the concentration of albumin in the emulsion is from about 8 mg / mL to about 200 mg / mL.

[0038] In some embodiments of the emulsion, the phase fraction of the organic phase in the emulsion is from about 1% to about 20%.

[0039] In some embodiments of the emulsion, the nanodroplets have a Z-average diameter of about 200 nm or less, hi some embodiments, the nanodroplets have a Z-average diameter of about 50 nm to about 200 nm.

[0040] In some embodiments of the emulsion, the Z-average particle size of the nanodroplets does not increase by more than 30% after storing the emulsion at 4° C. for about 4 hours.

[0041] In some embodiments of the emulsion, the albumin is human albumin.

[0042] Methods for preparing nanoparticle suspensions are also described herein. The methods can include removing organic solvent from an emulsion comprising a dispersed organic phase containing nanodroplets containing rapamycin dissolved in an organic solvent comprising chloroform and tert-butanol, and a continuous aqueous phase containing albumin, to prepare the nanoparticle suspension. In some embodiments, the organic solvent is removed using a wiped-film evaporator or a rotary evaporator. The evaporator can be a continuous evaporator or a batch evaporator. A continuous evaporator is an evaporator in which the feed and product streams are continuous and their concentrations remain generally constant due to consistent input to the feed stream. A batch evaporator is an evaporator in which the feed and product streams are discontinuous. In some embodiments, the organic solvent is removed using a continuous evaporator. In some embodiments, the organic solvent is removed using a batch evaporator. In some embodiments, the method further includes forming an emulsion by homogenizing the organic and aqueous phases.

[0043] In some embodiments for preparing a nanoparticle suspension, the organic solvent comprises about 10% to about 50% by volume of tert-butanol. In some embodiments, the organic solvent comprises about 50% to about 90% by volume of chloroform. In some embodiments, the organic solvent comprises chloroform and tert-butanol in a volume ratio of about 1:1 to about 9:1. In some embodiments, the concentration of rapamycin in the organic phase is about 20 mg / mL to about 500 mg / mL. In some embodiments, the concentration of rapamycin in the emulsion is about 2 mg / mL to about 50 mg / mL. In some embodiments, the concentration of albumin in the aqueous phase is about 10 mg / mL to about 200 mg / mL. In some embodiments, the concentration of albumin in the emulsion is about 8 mg / mL to about 200 mg / mL. In some embodiments, the organic phase fraction in the emulsion is about 1% to about 20%. In some embodiments, the nanodroplets have a Z-average particle size of about 200 nm or less. In some embodiments, the nanodroplets have a Z-average particle size of about 50 nm to about 200 nm. In some embodiments, the albumin is human albumin.

[0044] In some embodiments of preparing a nanoparticle suspension, prior to removing the organic solvent, the emulsion is stored at about 2° C. to about 8° C. In some embodiments, the emulsion is stored for about 4 hours or about 24 hours.

[0045] In some embodiments of preparing a nanoparticle suspension, the method further comprises filtering the organic phase, the aqueous phase, or both, prior to forming the emulsion.

[0046] In some embodiments of preparing a nanoparticle suspension, the organic and aqueous phases are homogenized using a high-pressure homogenizer.

[0047] In some embodiments of preparing a nanoparticle suspension, the method further comprises adding a solution comprising albumin to the nanoparticle suspension, in some embodiments, the addition of the solution comprising albumin adjusts the weight ratio of albumin to rapamycin in the nanoparticle suspension to between about 1:1 and about 10:1.

[0048] In some embodiments of preparing a nanoparticle suspension, the method further comprises filtering the nanoparticle suspension.

[0049] In some embodiments of preparing a nanoparticle suspension, the method further comprises lyophilizing the nanoparticle suspension. In some embodiments of preparing a nanoparticle suspension, the method further comprises adding the nanoparticle suspension to one or more vials. In some embodiments, the method comprises lyophilizing the nanoparticle suspension after adding the nanoparticle suspension to the one or more vials.

[0050] Also described herein are methods for assessing the suitability of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin and (b) a non-nanoparticle portion comprising albumin and rapamycin for medical use in a human individual, the method comprising measuring a quality control parameter for the pharmaceutical composition; and assessing the suitability of the pharmaceutical composition for medical use in a human individual, wherein a measured quality control parameter that is within a quality control threshold indicates the suitability of the pharmaceutical composition for medical use. In some embodiments, the method further comprises separating the nanoparticles from the non-nanoparticle portion, and the quality control parameter comprises a quality control parameter for the nanoparticle or the non-nanoparticle portion. In some embodiments, the nanoparticles comprise a core comprising rapamycin and a coating comprising albumin. The quality control parameter can be any or a combination of the parameters described herein for nanoparticle compositions, for example, assessed by the corresponding methods described herein.

[0051] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the nanoparticle portion that is in the form of monomeric albumin of the total albumin in the nanoparticle portion; a weight percent of albumin in the nanoparticle portion that is in the form of monomeric albumin of the total albumin in the nanoparticle portion of about 70% to about 85% indicates suitability of the pharmaceutical composition for medical use.

[0052] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the form of polymeric albumin in the nanoparticle portion of the total albumin in the nanoparticle portion; a weight percent of albumin in the form of polymeric albumin in the nanoparticle portion of the total albumin in the nanoparticle portion of about 5% to about 15% indicates suitability of the pharmaceutical composition for medical use.

[0053] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the nanoparticle portion that is in the form of dimeric albumin of the total albumin in the nanoparticle portion; a weight percent of albumin in the nanoparticle portion that is in the form of dimeric albumin of the total albumin in the nanoparticle portion of about 9% to about 20% indicates suitability of the pharmaceutical composition for medical use.

[0054] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight % of albumin in the form of polymeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion; a weight % of albumin in the form of polymeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion of about 0.5% to about 5% indicates suitability of the pharmaceutical composition for medical use.

[0055] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the non-nanoparticle portion that is in the form of monomeric albumin of the total albumin in the non-nanoparticle portion; a weight percent of albumin in the non-nanoparticle portion that is in the form of monomeric albumin of the total albumin in the non-nanoparticle portion of about 80% to about 95% indicates suitability of the pharmaceutical composition for medical use.

[0056] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the form of dimeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion; a weight percent of albumin in the form of dimeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion of about 4% to about 15% indicates suitability of the pharmaceutical composition for medical use.

[0057] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the form of polymeric albumin in the composition of the total albumin in the composition; and a weight percent of albumin in the form of polymeric albumin in the composition of the total albumin in the composition of about 0.5% to about 5% indicates the suitability of the pharmaceutical composition for medical use.

[0058] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the composition that is in the form of monomeric albumin of the total albumin in the composition; and a weight percent of albumin in the composition that is in the form of monomeric albumin of the total albumin in the composition of about 80% to about 95% indicates the suitability of the pharmaceutical composition for medical use.

[0059] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the composition that is in the form of dimeric albumin of the total albumin in the composition; and a weight percent of albumin in the composition that is in the form of dimeric albumin of the total albumin in the composition of about 4% to about 15% indicates the suitability of the pharmaceutical composition for medical use.

[0060] In some embodiments of assessing the suitability of a pharmaceutical composition, the percentage of polymeric, dimeric, or monomeric albumin is measured using size exclusion chromatography.

[0061] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the volume-weighted mean particle size of the nanoparticles; a volume-weighted mean particle size of the nanoparticles of about 200 nm or less indicates the suitability of the pharmaceutical composition for medical use.

[0062] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the volume-weighted mean particle size of the nanoparticles; a volume-weighted mean particle size of the nanoparticles of about 50 nm to about 200 nm indicates the suitability of the pharmaceutical composition for medical use.

[0063] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the Z-average particle size of the nanoparticles; a Z-average particle size of the nanoparticles of about 200 nm or less indicates the suitability of the pharmaceutical composition for medical use.

[0064] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the Z-average particle size of the nanoparticles; a Z-average particle size of about 50 nm to about 200 nm indicates the suitability of the pharmaceutical composition for medical use.

[0065] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the polydispersity index of the nanoparticles; a polydispersity index of the nanoparticles of less than 0.3 indicates the suitability of the pharmaceutical composition for medical use.

[0066] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the polydispersity index of the nanoparticles; a polydispersity index of the nanoparticles of about 0.03 to about 0.3 indicates the suitability of the pharmaceutical composition for medical use.

[0067] In some embodiments, in assessing the suitability of a pharmaceutical composition, the quality control parameter is the size distribution range of the nanoparticles ((D v 95-D v 5) / D v 50); a particle size distribution range of the nanoparticles of about 1.2 or less indicates suitability of the pharmaceutical composition for medical use.

[0068] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight percent of albumin in the nanoparticle portion; a weight percent of albumin in the nanoparticle portion of about 25% to about 45% indicates the suitability of the pharmaceutical composition for medical use.

[0069] In some embodiments for assessing the suitability of the pharmaceutical composition, the quality control parameters include the weight percent of rapamycin in the nanoparticle portion; a weight percent of rapamycin in the nanoparticle portion of about 55% to about 75% indicates the suitability of the pharmaceutical composition for medical use.

[0070] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight ratio of albumin to rapamycin in the nanoparticle portion; a weight ratio of albumin to rapamycin in the nanoparticle portion of about 1:1 to about 1:4 indicates the suitability of the pharmaceutical composition for medical use.

[0071] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the weight ratio of albumin to rapamycin in the composition; a weight ratio of albumin to rapamycin in the composition of about 1:1 to about 10:1 indicates the suitability of the pharmaceutical composition for medical use.

[0072] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the percentage of albumin in the composition of the non-nanoparticle portion; a percentage of albumin in the composition of the non-nanoparticle portion of about 95% or greater indicates the suitability of the pharmaceutical composition for medical use.

[0073] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the percentage of rapamycin in the composition of the nanoparticle portion; a percentage of rapamycin in the composition of the nanoparticle portion of about 98% or greater indicates the suitability of the pharmaceutical composition for medical use.

[0074] In some embodiments for assessing the suitability of a pharmaceutical composition, the pharmaceutical composition is a nanoparticle suspension.

[0075] In some embodiments for assessing the suitability of a pharmaceutical composition, the pharmaceutical composition is reconstituted from a dry nanoparticle composition, such as a powder.

[0076] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the concentration of albumin in the composition; a concentration of albumin in the composition of about 30 mg / mL to about 100 mg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0077] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the concentration of albumin in the non-nanoparticle portion composition; a concentration of albumin in the non-nanoparticle portion composition of about 30 mg / mL to about 100 mg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0078] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the concentration of albumin in the nanoparticle portion composition; a concentration of albumin in the nanoparticle portion composition of about 1.8 mg / mL to about 15 mg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0079] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the concentration of rapamycin in the composition; a concentration of rapamycin in the composition of about 1 mg / mL to about 15 mg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0080] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the concentration of rapamycin in the non-nanoparticle portion composition; a concentration of rapamycin in the non-nanoparticle portion composition of about 20 μg / mL to about 55 μg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0081] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the concentration of rapamycin in the nanoparticle portion composition; a concentration of rapamycin in the nanoparticle portion composition of about 1 mg / mL to about 15 mg / mL indicates the suitability of the pharmaceutical composition for medical use.

[0082] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the osmolality of the composition; an osmolality of the composition of about 300 mOSm / kg to about 350 mOSm / kg indicates the suitability of the pharmaceutical composition for medical use.

[0083] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the viscosity of the composition; a viscosity of the composition of about 1.2 cP to about 1.5 cP indicates the suitability of the pharmaceutical composition for medical use.

[0084] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the stability of the composition; the stability of the composition for at least 24 hours at 25° C. indicates the suitability of the pharmaceutical composition for medical use.

[0085] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the stability of the composition; the stability of the composition for at least 24 hours at 4° C. indicates the suitability of the pharmaceutical composition for medical use.

[0086] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the pH of the composition; a pH of the composition of about 6.0 to about 7.5 indicates the suitability of the pharmaceutical composition for medical use.

[0087] In some embodiments of assessing the suitability of a pharmaceutical composition, the composition is prepared with tert-butanol and the quality control parameter comprises the concentration of tert-butanol; a concentration of tert-butanol less than 10 μg / mL of tert-butanol indicates the suitability of the pharmaceutical composition for medical use.

[0088] In some embodiments for assessing the suitability of a pharmaceutical composition, the composition is prepared using chloroform and the quality control parameter comprises the concentration of chloroform; a concentration of chloroform less than 5 μg / mL chloroform indicates the suitability of the pharmaceutical composition for medical use.

[0089] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the zeta potential of the nanoparticles; a zeta potential of the nanoparticles of about -25 mV to about -50 mV indicates the suitability of the pharmaceutical composition for medical use.

[0090] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the morphology of the composition, where the morphology is determined by measuring the crystallinity of a lyophilized form of the composition by X-ray diffraction; an amorphous form of the composition indicates the suitability of the pharmaceutical composition for medical use.

[0091] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the morphology of the composition, which is measured by isolating the nanoparticles from the composition, lyophilizing the isolated nanoparticles, and measuring the crystallinity of the isolated and lyophilized nanoparticles by X-ray diffraction; an amorphous morphology of the composition indicates the suitability of the pharmaceutical composition for medical use.

[0092] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameters include the morphology of the composition, where the morphology is measured by Raman spectroscopy, differential scanning calorimetry (DSC), modulated differential scanning calorimetry (mDSC), Fourier transform infrared (FTIR) spectroscopy, or nuclear magnetic resonance (NMR) spectroscopy; and the amorphous morphology of the composition indicates the suitability of the pharmaceutical composition for medical use.

[0093] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises an interaction between the vinyl chain of rapamycin in the nanoparticle portion and albumin in the nanoparticle portion; an identified interaction between the vinyl chain of rapamycin in the nanoparticle portion and albumin in the nanoparticle portion indicates the suitability of the pharmaceutical composition for medical use.

[0094] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter comprises the percentage of nanoparticles that are non-spherical; identification of at least a portion of the nanoparticles as non-spherical indicates the suitability of the pharmaceutical composition for medical use.

[0095] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the percentage of nanoparticles that are non-spherical; identification of at least 20% of the nanoparticles as non-spherical indicates the suitability of the pharmaceutical composition for medical use.

[0096] In some embodiments for assessing the suitability of a pharmaceutical composition, quality control parameters include the weight percent of seco-rapamycin compared to the sum of seco-rapamycin and rapamycin in the nanoparticle portion; a weight percent of seco-rapamycin compared to the sum of seco-rapamycin and rapamycin in the nanoparticle portion of less than 2.5% seco-rapamycin indicates suitability of the pharmaceutical composition for medical use.

[0097] In some embodiments for assessing the suitability of a pharmaceutical composition, the quality control parameter includes the percentage of rapamycin in the pharmaceutical composition that is free rapamycin; a percentage of rapamycin in the pharmaceutical composition that is free rapamycin of less than 3% indicates suitability of the pharmaceutical composition for medical use.

[0098] In some embodiments for assessing the suitability of a pharmaceutical composition, the albumin is human albumin.

[0099] Also provided herein is a method of releasing a commercial batch of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticulate portion comprising albumin and rapamycin, the method comprising using a sample of the commercial batch to evaluate the suitability of the pharmaceutical composition for medical use in a human individual, and releasing the commercial batch if the pharmaceutical composition is suitable for medical use.

[0100] Further provided herein is a method of processing a sample of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticulate portion comprising albumin and rapamycin to confirm the sample is suitable for medical use in a human individual, the method comprising obtaining the sample from a commercial batch; and using the sample from the commercial batch to evaluate the suitability of the pharmaceutical composition for medical use in a human individual.

[0101] Also described is a method for preparing a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin and (b) a non-nanoparticulate portion comprising albumin and rapamycin for sale, the method comprising: evaluating the suitability of the pharmaceutical composition for medical use in a human individual; identifying the pharmaceutical composition as suitable for medical use in a human individual; and packaging the pharmaceutical composition for sale. In some embodiments, packaging the pharmaceutical composition comprises lyophilizing the pharmaceutical composition. In some embodiments, packaging the pharmaceutical composition comprises filling the pharmaceutical composition into a container. In some embodiments, the method comprises sealing the container. [Brief explanation of the drawings]

[0102] [Figure 1] Figure 1 shows cryo-TEM images at 52,000x magnification (0.21 nm / pixel) of lot #11 (top left), lot #1 (top right), lot #3 (center left), human albumin alone (center right), or lot #2 (bottom).

[0103] [Figure 2] Figure 2 shows a cryo-TEM image at 21,000x magnification of lot #11, in which irregularly shaped particles with non-uniform internal density (bottom arrow), spherical particles with uniform density (top left arrow), and small round-shaped particles (top right arrow) were observed.

[0104] [Figure 3] Figure 3 shows a cryo-TEM image at 21,000x magnification of lot #1, in which irregularly shaped particles with non-uniform internal density (upper arrow), spherical particles with uniform density (lower arrow), and small round-shaped particles (center arrow) were observed.

[0105] [Figure 4]4 shows a representative chromatogram of a pharmaceutical composition comprising rapamycin and albumin (Lot #1 after 12 months of storage at 5° C.) as measured by size exclusion chromatography (SEC). Peaks corresponding to monomers, dimers, polymers, and oligomers (which can be identified by a suitable technique, such as mass spectrometry) are shown in the chromatogram.

[0106] [Figure 5] Figure 5 shows the light scattering intensity (kcps) as a function of rapamycin concentration from a reconstituted suspension of a pharmaceutical composition containing nanoparticles containing rapamycin and albumin. When the suspension was diluted to a concentration below the solubility of rapamycin, the nanoparticles completely disintegrated and dissolved (see data points 7-8 on the left on the graph). However, when the suspension was diluted to a concentration above the solubility of rapamycin, the nanoparticles only partially disintegrated and dissolved, and light scattering was observed (see data points 4-5 on the right on the graph). The light scattering intensity increased linearly with increasing rapamycin concentration above the solubility point of rapamycin (calculated to be 16.1 ± 1.8 μg / mL in 0.9% saline solution).

[0107] [Figure 6] FIG. 6 shows the dissolution profile of a reconstituted suspension of a pharmaceutical composition comprising nanoparticles comprising rapamycin and albumin (Lot #2; stored at 5° C. for 32 months before reconstitution) at a rapamycin concentration of 5 μg / ml (top line) or 25 μg / ml (bottom line).

[0108] [Figure 7] FIG. 7 shows the dissolution profiles of reconstituted suspensions of a pharmaceutical composition comprising nanoparticles containing rapamycin and albumin (Lot #2; stored at 25° C. / 60% RH for 32 months before reconstitution) at rapamycin concentrations of 5 μg / ml (top line) or 25 μg / ml (bottom line).

[0109] [Figure 8]FIG. 8 shows the dissolution profile of a reconstituted suspension of a pharmaceutical composition (Lot #4) comprising nanoparticles comprising rapamycin and albumin at a rapamycin concentration of 5 μg / ml (top line) or 25 μg / ml (bottom line).

[0110] [Figure 9] Figure 9 shows the SEC-UV chromatogram of the oligomeric profile of total human albumin in rapamycin nanoparticle pharmaceuticals. The peak labeled "polymer" corresponds to albumin polymers other than oligomers.

[0111] [Figure 10] Figure 10 shows a SEC-UV chromatogram of the oligomer profile of the non-nanoparticle portion of human albumin in a rapamycin nanoparticle pharmaceutical. The peak labeled "polymer" corresponds to the non-oligomer albumin polymer.

[0112] [Figure 11] 11 shows a SEC-UV chromatogram of the oligomer profile of the nanoparticle portion of human albumin in a rapamycin nanoparticle pharmaceutical. The peak labeled "polymer" corresponds to albumin polymers other than oligomers. DETAILED DESCRIPTION OF THE INVENTION

[0113] Nanoparticle compositions (e.g., pharmaceutical compositions) comprising albumin and rapamycin, or commercial batches of nanoparticle compositions, are described herein. The nanoparticles comprise albumin and rapamycin associated with each other within the nanoparticles. For example, the nanoparticles may comprise a coating comprising albumin and a core comprising rapamycin. The composition may further comprise a non-nanoparticle portion comprising albumin and rapamycin that is not contained within the nanoparticle portion. That is, the composition may comprise nanoparticle-bound albumin and nanoparticle-bound rapamycin in the nanoparticle portion of the composition and non-nanoparticle albumin and non-nanoparticle rapamycin in the non-nanoparticle portion of the composition. As used herein, "in nanoparticles" is used synonymously with "in nanoparticle portion."

[0114] Further described herein is a stable emulsion comprising organic phase nanodroplets containing an organic solvent and rapamycin dispersed in a continuous aqueous phase containing albumin. The emulsion can be used to produce a nanoparticle composition by removing the organic solvent from the emulsion, for example, according to the manufacturing methods described herein.

[0115] Furthermore, a quality control process for pharmaceutical preparations is described herein, which can be used to ensure that a pharmaceutical composition is suitable for medical use in human individuals. For example, a pharmaceutical composition can be subjected to a quality control process before a commercial batch of the pharmaceutical composition is released, which helps to ensure the safety and efficacy of the pharmaceutical composition. This process can include measuring a quality control parameter of the composition (i.e., a distinctive characteristic of the composition that indicates its suitability for medical use) and comparing the measured quality control parameter with a quality control threshold. If the measured parameter is within the threshold, this comparison indicates that the pharmaceutical composition is suitable for medical use in human individuals.

[0116] A nanoparticle composition (e.g., a pharmaceutical composition) described herein, or a commercial batch of a nanoparticle composition (e.g., a pharmaceutical composition), may have distinct characteristics with respect to any one or more (any combination) of the following: (1) the oligomeric state of albumin associated with (e.g., within) the nanoparticles, such as the proportion of albumin monomers, dimers, oligomers, and / or polymers (or polymers other than oligomers) of albumin associated with (e.g., within) the nanoparticles; (2) the albumin monomers of albumin associated with (e.g., within) the non-nanoparticle portion of the composition. (3) the oligomeric state of the total albumin in the composition, such as the percentage of albumin monomers, dimers, oligomers, and / or polymers (or polymers other than oligomers) of the total albumin in the composition; (4) the particle size profile of the nanoparticles, such as the mean particle size, polydispersity index, and / or particle size distribution; (5) the percentage of nanoparticles that are albumin (e.g., heavy or light); (6) the weight ratio of albumin to rapamycin in the nanoparticles; (7) the weight ratio of albumin to rapamycin in the non-nanoparticle portion of the composition; (8) the weight ratio of albumin to rapamycin in the non-nanoparticle portion of the composition; (9) the weight ratio of total albumin to total rapamycin in the composition; (10) the percentage (e.g., weight %) of rapamycin that is in the nanoparticles (or non-nanoparticle portion of the composition) compared to the total rapamycin in the composition; (11) the total albumin in the composition (12) the concentration of albumin in the composition; (13) the concentration of albumin in the non-nanoparticle portion of the composition; (14) the concentration of albumin in the composition associated with (e.g., in) nanoparticles; (15) the concentration of rapamycin in the composition; (16) the concentration of rapamycin in the non-nanoparticle portion of the composition; (17) the concentration of rapamycin in the composition associated with (e.g., in) nanoparticles; (18) the osmolality of the composition; (19) the viscosity of the composition; (20) the pH of the composition;(21) stability of the nanoparticles in the composition; (22) amount of residual solvent in the composition; (23) zeta potential of the nanoparticles in the composition; (24) crystalline state of the rapamycin in the nanoparticles; (25) particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) weight percent of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin by weight; (27) presence, proportion, or concentration of albumin stabilizer (such as caprylic acid derivatives, e.g., sodium caprylate and / or tryptophan derivatives, e.g., N-acetyltryptophanate) in the composition; (28) recovery of rapamycin after filtration; (29) in vitro release kinetics of the nanoparticles; and / or (30) percentage of total rapamycin in the composition that is in the non-nanoparticle portion of the composition and not bound to albumin. The physicochemical parameters discussed above affect the drug release and delivery of albumin-based rapamycin nanoparticle compositions (e.g., pharmaceutical compositions) and may therefore constitute unique properties of the compositions;

[0117] A nanoparticle composition (e.g., a pharmaceutical composition) described herein, or a commercial batch of a nanoparticle composition (e.g., a pharmaceutical composition), can have distinct characteristics with respect to any one or more (any combination) of the following: (1) the oligomeric state of albumin associated with (e.g., within) the nanoparticles, such as the proportion of albumin monomers, dimers, and / or polymers (e.g., trimers) of albumin associated with (e.g., within) the nanoparticles; (2) the proportion of albumin monomers, dimers, and / or trimers of albumin associated with (e.g., within) the non-nanoparticle portion of the composition. (3) the oligomeric state of the total albumin in the composition, such as the percentage of albumin monomer, dimer, and / or trimer of the total albumin in the composition; (4) the particle size profile of the nanoparticles, such as the mean particle size, polydispersity index, and / or particle size distribution; (5) the percentage (e.g., weight %) of the nanoparticles that are albumin and / or the percentage (e.g., weight %) of the nanoparticles that are rapamycin; (6) the weight ratio of albumin to rapamycin in the nanoparticles; (7) the ratio of albumin to rapamycin in the nanoparticles; (8) the weight ratio of albumin to rapamycin in the non-nanoparticle portion of the composition; (9) the weight ratio of total albumin to total rapamycin in the composition; (10) the percentage (e.g., weight %) of rapamycin that is in the nanoparticles (or non-nanoparticle portion of the composition) compared to the total rapamycin in the composition; (11) the percentage (e.g., weight %) of albumin that is in the non-nanoparticle portion (or in the nanoparticles) compared to the total albumin in the composition; (12) the concentration of albumin in the composition; (13) the percentage (e.g., weight %) of albumin in the non-nanoparticle portion of the composition. (14) the concentration of albumin in the composition associated with (e.g., in) the nanoparticles; (15) the concentration of rapamycin in the composition; (16) the concentration of rapamycin in the non-nanoparticle portion of the composition; (17) the concentration of rapamycin in the composition associated with (e.g., in) the nanoparticles; (18) the osmolality of the composition; (19) the viscosity of the composition; (20) the pH of the composition; (21) the stability of the nanoparticles in the composition; (22) the amount of residual solvent in the composition; (23) the zeta potential of the nanoparticles in the composition; (24) the crystalline state of the rapamycin in the nanoparticles;(25) particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) weight percent of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin by weight; (27) the presence, proportion, or concentration of an albumin stabilizer (such as a caprylic acid derivative, e.g., sodium caprylate, and / or a tryptophan derivative, e.g., N-acetyltryptophanate) in the composition; (28) recovery of rapamycin after filtration; (29) in vitro release kinetics of the nanoparticles; and / or (30) the percentage of total rapamycin in the composition that is in the non-nanoparticle portion of the composition and not bound to albumin. The physicochemical parameters discussed above affect drug release and delivery from albumin-based rapamycin nanoparticle compositions (e.g., pharmaceutical compositions) and may therefore constitute unique characteristics of the composition.

[0118] The emulsions described herein (such as those in commercial batches) comprise organic phase nanodroplets containing an organic solvent (such as chloroform and / or tert-butanol) and rapamycin dispersed in a continuous aqueous phase containing albumin. Such emulsions can have distinct characteristics with respect to any one or more (any combination) of the following: (1) the proportion (e.g., volume percent) of a given solvent in the organic solvent mixture in the organic phase; (2) the relative ratio of two or more solvents in the organic solvent mixture in the organic phase; (3) the concentration of rapamycin in the organic phase; (4) the concentration of rapamycin in the emulsion; (5) the concentration of albumin in the aqueous phase of the emulsion; (6) the concentration of albumin in the emulsion; (7) the phase fraction of the organic phase in the emulsion; and / or (8) the particle size profile of the nanodroplets, such as the mean particle size, polydispersity index, and / or particle size distribution.

[0119] The compositions (e.g., pharmaceutical compositions) or commercial batches of nanoparticle compositions (e.g., pharmaceutical compositions) disclosed herein are useful for treating various diseases, such as cancer. Accordingly, methods of using such compositions (e.g., pharmaceutical compositions) to treat diseases, including cancer, are further provided herein. Kits, commercial batches, medicaments, and dosage forms comprising the compositions (e.g., pharmaceutical compositions) described herein and for use in the methods described herein are also provided.

[0120] Certain exemplary embodiments provided herein disclose pharmaceutical compositions. It should be understood that these are exemplary compositions, and that these descriptions equally apply to and describe other compositions of the invention provided herein, including compositions having any of the characteristics defined in these exemplary embodiments.

[0121] Throughout this application, characteristics and properties of albumin-based rapamycin nanoparticle compositions are described and defined. These characteristics and properties are also described, in certain embodiments, as quality control parameters. Throughout these descriptions, the composition may be in the form of a manufactured lot of the composition. It is understood that evaluation of a sample of the lot (e.g., a single vial from a lot containing multiple vials, etc.) can be used to assess a characteristic or property of the composition throughout the manufactured lot. Alternatively, in some embodiments, multiple samples of a manufactured lot can be evaluated and the results averaged to assess a particular characteristic or property of the entire lot. Unless otherwise specified, references to "composition," "pharmaceutical composition," and / or "commercial batch," etc., include reference to a manufactured lot of the composition, pharmaceutical composition, commercial batch, etc.

[0122] definition As used in this specification and the appended claims, the singular forms "a," "or," and "the" include plural referents unless the context clearly requires otherwise.

[0123] Reference herein to "about" a value or parameter includes (and describes) a variation on that value or parameter itself. For example, a description referring to "about X" includes a description of "X." Furthermore, as used herein, the term "about X to Y" has the same meaning as "about X to about Y." Alternatively, the use of "about" preceding any series of numbers includes "about" each of the recited numbers in that series. For example, a description referring to "about X, Y, or Z" is intended to describe "about X, about Y, or about Z."

[0124] "Albumin dimer" or "dimeric albumin" refers to an albumin species that has two, and only two, albumin units.

[0125] "Albumin monomer" or "monomeric albumin" refers to an albumin species having one, and only one, albumin unit.

[0126] "Albumin polymer" or "polymeric albumin" refers to an albumin species that has a higher molecular weight than albumin monomer and albumin dimer.

[0127] "Albumin trimer" or "trimeric albumin" refers to an albumin species having three, and only three, albumin units.

[0128] "Albumin oligomers" refers to low molecular weight polymeric albumin species associated with UV absorbance-based size-exclusion chromatographic peaks observed between those associated with albumin dimers and those associated with high molecular weight polymeric albumin species. Figures 9-11 show exemplary size-exclusion chromatograms with peaks labeled for monomers, dimers, oligomers, and polymers (non-oligomers).

[0129] "Free rapamycin" is used to describe the rapamycin in the composition that is not in nanoparticles and that is not bound to albumin in the non-nanoparticle portion of the composition.

[0130] A material described as "in a nanoparticle" refers to a material that is part of a nanoparticle in any arrangement. Thus, the material may be coated on the surface of the nanoparticle, in the core of the nanoparticle, or embedded within the nanoparticle, or a mixture thereof. A material described as being "in the non-nanoparticle portion" of the composition refers to a material in the composition that is not "in the nanoparticle."

[0131] The term "individual" refers to a mammal, including, but not limited to, a human, bovine, equine, feline, canine, rodent, or primate.

[0132] The term "nanoparticle" is used herein to refer to a solid particle. The term "nanodroplet" is used herein to refer to a liquid particle, for example in the context of an oil-in-water or other emulsion.

[0133] Aspects and embodiments described herein are understood to include "consisting of" and / or "consisting essentially of" aspects and embodiments.

[0134] It is understood that references to relative percentages in a composition assume that the combined total percentages of all components in the composition total 100. The relative percentage of one or more components can be adjusted higher or lower so that the combined percentages of the components in the composition total 100, provided that the percentage of any particular component does not exceed the limits of the range specified for that component.

[0135] Albumin-Based Nanoparticle Compositions The nanoparticle composition, or commercial batch of nanoparticle composition, described herein comprises (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticle portion comprising rapamycin and albumin. The rapamycin and albumin of the nanoparticles are associated with each other within the nanoparticles. For example, the nanoparticles may comprise a coating having albumin surrounding a core comprising rapamycin. In the non-nanoparticle portion of the composition, the rapamycin and albumin may or may not be associated with each other (i.e., rapamycin may be in reversible binding equilibrium with albumin), but are not associated with each other in a manner that forms nanoparticles. The albumin of the nanoparticles may be further distinguished from the albumin in the non-nanoparticle portion of the composition; for example, the oligomeric profile of albumin in the nanoparticles may be different from the oligomeric profile of albumin in the non-nanoparticle portion of the composition.

[0136] The albumin of the nanoparticles associates with the rapamycin of the nanoparticles such that the nanoparticle suspension has a high concentration of rapamycin, thereby enabling the composition to be used as a pharmaceutical composition for treating certain diseases, such as cancer. The produced nanoparticles (which may be prepared, for example, using the methods described herein) can be formulated, filtered, or otherwise processed to obtain a pharmaceutical composition that may be suitable for medical use in human individuals.

[0137] A nanoparticle composition (e.g., a pharmaceutical composition) described herein, or a commercial batch of a nanoparticle composition (e.g., a pharmaceutical composition), may have distinct characteristics with respect to any one or more (any combination) of the following: (1) the oligomeric state of albumin associated with (e.g., within) the nanoparticles, such as the proportion of albumin monomers, dimers, oligomers, and / or polymers (or polymers other than oligomers) of albumin associated with (e.g., within) the nanoparticles; (2) the albumin monomers of albumin associated with (e.g., within) the non-nanoparticle portion of the composition. (3) the oligomeric state of the total albumin in the composition, such as the percentage of albumin monomers, dimers, oligomers, and / or polymers (or polymers other than oligomers) of the total albumin in the composition; (4) the particle size profile of the nanoparticles, such as the mean particle size, polydispersity index, and / or particle size distribution; (5) the percentage of nanoparticles that are albumin (e.g., heavy or light); (6) the weight ratio of albumin to rapamycin in the nanoparticles; (7) the weight ratio of albumin to rapamycin in the non-nanoparticle portion of the composition; (8) the weight ratio of albumin to rapamycin in the non-nanoparticle portion of the composition; (9) the weight ratio of total albumin to total rapamycin in the composition; (10) the percentage (e.g., weight %) of rapamycin that is in the nanoparticles (or non-nanoparticle portion of the composition) compared to the total rapamycin in the composition; (11) the total albumin in the composition (12) the concentration of albumin in the composition; (13) the concentration of albumin in the non-nanoparticle portion of the composition; (14) the concentration of albumin in the composition associated with (e.g., in) nanoparticles; (15) the concentration of rapamycin in the composition; (16) the concentration of rapamycin in the non-nanoparticle portion of the composition; (17) the concentration of rapamycin in the composition associated with (e.g., in) nanoparticles; (18) the osmolality of the composition; (19) the viscosity of the composition; (20) the pH of the composition;(21) stability of the nanoparticles in the composition; (22) amount of residual solvent in the composition; (23) zeta potential of the nanoparticles in the composition; (24) crystalline state of the rapamycin in the nanoparticles; (25) particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) weight percent of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin by weight; (27) presence, proportion, or concentration of an albumin stabilizer (such as sodium caprylate and / or N-acetyltryptophanate) in the composition; (28) recovery of rapamycin after filtration; (29) in vitro release kinetics of the nanoparticles; and / or (30) percentage of total rapamycin in the composition that is in the non-nanoparticulate portion of the composition and not bound to albumin.

[0138] A nanoparticle composition (e.g., a pharmaceutical composition) described herein, or a commercial batch of a nanoparticle composition (e.g., a pharmaceutical composition), can be characterized by any one or more (any combination) of the following: (1) the oligomeric state of albumin associated with (e.g., within) the nanoparticles, such as the percentage of albumin monomer, dimer, and / or trimer of albumin associated with (e.g., within) the nanoparticles; (2) the percentage of albumin monomer, dimer, and / or trimer of albumin associated with (e.g., within) the non-nanoparticle portion of the composition, such as (3) the oligomeric state of the total albumin in the composition, such as the percentage of albumin monomer, dimer, and / or trimer of the total albumin in the composition; (4) the particle size profile of the nanoparticles, such as the mean particle size, polydispersity index, and / or particle size distribution; (5) the percentage (e.g., weight %) of the nanoparticles that are albumin and / or the percentage (e.g., weight %) of the nanoparticles that are rapamycin; (6) the weight ratio of albumin to rapamycin in the nanoparticles; (7) the percentage (e.g., weight %) of the nanoparticles that are albumin and / or rapamycin in the composition; (8) the weight ratio of albumin to rapamycin in the non-nanoparticulate portion of the composition; (9) the weight ratio of total albumin to total rapamycin in the composition; (10) the percentage (e.g., weight %) of rapamycin that is in the nanoparticles (or non-nanoparticulate portion of the composition) compared to the total rapamycin in the composition; (11) the percentage (e.g., weight %) of albumin that is in the non-nanoparticulate portion (or in the nanoparticles) compared to the total albumin in the composition; (12) the concentration of albumin in the composition; (13) the non-nanoparticulate portion of the composition (14) the concentration of albumin in the composition associated with (e.g., in) the nanoparticles; (15) the concentration of rapamycin in the composition; (16) the concentration of rapamycin in the non-nanoparticle portion of the composition; (17) the concentration of rapamycin in the composition associated with (e.g., in) the nanoparticles; (18) the osmolality of the composition; (19) the viscosity of the composition; (20) the pH of the composition; (21) the stability of the nanoparticles in the composition; (22) the amount of residual solvent in the composition; (23) the zeta potential of the nanoparticles in the composition; (24) the crystalline state of the rapamycin in the nanoparticles;(25) particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) weight percent of seco-rapamycin in the nanoparticles compared to the sum of seco-rapamycin and rapamycin, by weight; (27) the presence, proportion, or concentration of albumin stabilizers (such as caprylic acid derivatives, e.g., sodium caprylate and / or tryptophan derivatives, e.g., N-acetyltryptophanate) in the composition; (28) recovery of rapamycin after filtration; (29) in vitro release kinetics of the nanoparticles; and / or (30) the percentage of total rapamycin in the composition that is in the non-nanoparticulate portion of the composition and not bound to albumin.

[0139] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, has one or more of the following defining characteristics: (1) about 80% to about 95% (or as further provided herein) of the total albumin in the composition is in the form of monomeric albumin; (2) about 4% to about 15% (or as further provided herein) of the total albumin in the composition is in the form of dimeric albumin; (3) about 0.5% to about 5% (or as further provided herein) of the total albumin in the composition is in the form of polymeric albumin (or trimeric albumin); (4) the weight ratio of total albumin to total rapamycin in the composition is about 1:1 to about 10:1 (or as further provided herein); (5) about 90% or more (or as further provided herein) of the total rapamycin in the composition is in nanoparticles; (6) about 90% or more (or as further provided herein) of the total albumin in the composition is in the non-nanoparticulate portion of the nanoparticles; (7) the composition comprises tert-butanol at a concentration of less than about 10 μg / mL or less than about 10 ppm (or as further provided herein); (8) the composition comprises chloroform at a concentration of less than about 5 μg / mL or less than about 5 ppm (or as further provided herein); (9) the composition comprises an albumin stabilizer (such as a caprylic acid derivative, e.g., sodium caprylate and / or a tryptophan derivative, e.g., N-acetyltryptophanate); (10) after filtering the composition using a 0.2 micron filter, at least about 80% or more (or as further provided herein) of the rapamycin in the composition is recoverable; (11) the composition is stable for at least 24 hours; and / or (12) less than about 5% of the total rapamycin in the composition is in the non-nanoparticulate portion of the composition and is not bound to albumin in the non-nanoparticulate portion of the composition.In some embodiments, the nanoparticle composition may be a nanoparticle suspension, and the nanoparticle composition may have one or more of the following defining characteristics (in addition to, or instead of, any one of the preceding defining characteristics): (1) the concentration of albumin in the composition is from about 30 mg / mL to about 100 mg / mL (or as further provided herein); (2) the concentration of rapamycin in the composition is from about 1 mg / mL to about 15 mg / mL (or from about 1 mg / mL to about 7 mg / mL, etc., as further provided herein); (3) the osmolality of the composition is from about 300 mOsm / kg to about 350 mOsm / kg (or as otherwise provided herein); (4) the viscosity of the composition is from about 1.2 cP to about 1.5 cP (or as otherwise provided herein); and / or (5) the pH of the composition is from about 6.0 to about 7.5 (or as otherwise provided herein).

[0140] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, has one or more of the following defining characteristics: (1) about 80% to about 95% (or as further provided herein) of the total albumin in the composition is in the form of monomeric albumin; (2) about 4% to about 15% (or as further provided herein) of the total albumin in the composition is in the form of dimeric albumin; (3) about 0.3% to about 3% of the total albumin in the composition is in the form of oligomeric albumin; (4) about 2% to about 7% (or as further provided herein) of the total albumin in the composition is in the form of polymeric albumin (other than oligomeric albumin); (5) the weight ratio of total albumin to total rapamycin in the composition is about 1:1 to about 10:1 (or as further provided herein); (6) about 90% or more (or as further provided herein) of the total rapamycin in the composition is in nanoparticles; (7) about 90% or more of the total albumin in the composition is in the form of dimeric albumin; (8) the composition comprises tert-butanol at a concentration of less than about 10 μg / mL or less than about 10 ppm (or as further provided herein); (9) the composition comprises chloroform at a concentration of less than about 5 μg / mL or less than about 5 ppm (or as further provided herein); (10) the composition comprises an albumin stabilizer (such as a caprylic acid derivative, e.g., sodium caprylate and / or a tryptophan derivative, e.g., N-acetyltryptophanate); (11) after filtering the composition using a 0.2 micron filter, at least about 80% or more (or as further provided herein) of the rapamycin in the composition is recoverable; (12) the composition is stable for at least 24 hours; and / or (13) less than about 5% of the total rapamycin in the composition is in the non-nanoparticulate portion of the composition, while not bound to albumin in the non-nanoparticulate portion of the composition.In some embodiments, the nanoparticle composition may be a nanoparticle suspension, and the nanoparticle composition may have one or more of the following defining characteristics (in addition to, or instead of, any one of the preceding defining characteristics): (1) the concentration of albumin in the composition is from about 30 mg / mL to about 100 mg / mL (or as further provided herein); (2) the concentration of rapamycin in the composition is from about 1 mg / mL to about 15 mg / mL (or from about 1 mg / mL to about 7 mg / mL, etc., as further provided herein); (3) the osmolality of the composition is from about 300 mOsm / kg to about 350 mOsm / kg (or as otherwise provided herein); (4) the viscosity of the composition is from about 1.2 cP to about 1.5 cP (or as otherwise provided herein); and / or (5) the pH of the composition is from about 6.0 to about 7.5 (or as otherwise provided herein).

[0141] In some embodiments, the nanoparticles of the composition, or of a commercial batch of the composition, have one or more of the following defining characteristics: (1) about 70% to about 85% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin monomer; (2) about 9% to about 20% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin dimer; (3) about 5% to about 15% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin polymer (or albumin trimer); (4) the nanoparticles have a volume-weighted average particle size and / or Z-average particle size of about 200 nm or less (or about 50 nm to about 200 nm, etc., as otherwise provided herein); (5) the nanoparticles have a polydispersity index of less than about 0.2 (or about 0.03 to about 0.2, etc., as otherwise provided herein); (6) a particle size distribution range (D v95 -D v5 ) / D v50(7) the nanoparticles are about 25% to about 45% by weight (or as otherwise provided herein) albumin; (8) the nanoparticles are about 55% to about 75% by weight (or as otherwise provided herein) rapamycin; (9) the weight ratio of albumin to rapamycin in the nanoparticles is about 1:1 to about 1:4 (or as otherwise provided herein); (10) the zeta potential of the nanoparticles in the composition is about -25 mV to about -50 mV (or as otherwise provided herein); (11) the nanoparticles (12) the particles have an amorphous morphology; (13) the vinyl chains of the rapamycin in the nanoparticles interact with albumin in the nanoparticles; (14) at least a portion (e.g., at least 20%, or as otherwise provided herein) of the nanoparticles in the composition are non-spherical; and / or (15) the nanoparticles comprise less than about 2.5% by weight of seco-rapamycin (or about 0.2% to about 2.5% by weight, as otherwise provided herein) relative to the sum of seco-rapamycin and rapamycin. In some embodiments, the nanoparticle composition can be a nanoparticle suspension, and in some embodiments, the concentration of albumin in the nanoparticle suspension in the nanoparticles is about 1.8 mg / mL to about 3 mg / mL (or as otherwise provided herein).

[0142] In some embodiments, the nanoparticles of the composition, or the nanoparticles of a commercial batch of the composition, have one or more of the following defining characteristics: (1) about 25% to about 50% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin monomers; (2) about 5% to about 16% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin dimers; (3) about 1% to about 4.5% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin oligomers. (4) about 42% to about 60% (or as otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin polymers (other than albumin oligomers); (5) the nanoparticles have a volume-weighted average particle size and / or Z-average particle size of about 200 nm or less (or between about 50 nm and about 200 nm, as otherwise provided herein); (6) the nanoparticles have a polydispersity index of less than about 0.2 (or between about 0.03 and about 0.2, as otherwise provided herein); (7) a particle size distribution range (D v95 ~D v5 ) / D v50(8) the nanoparticles are about 25% to about 45% by weight (or as otherwise provided herein) albumin; (9) the nanoparticles are about 55% to about 75% by weight (or as otherwise provided herein) rapamycin; (10) the weight ratio of albumin to rapamycin in the nanoparticles is about 1:1 to about 1:4 (or as otherwise provided herein); (11) the zeta potential of the nanoparticles in the composition is about -25 mV to about -50 mV (or as otherwise provided herein); (12) the nanoparticles (13) the particles have an amorphous morphology; (14) the vinyl chains of the rapamycin in the nanoparticles interact with albumin in the nanoparticles; (15) at least a portion (e.g., at least 20%, or as otherwise provided herein) of the nanoparticles in the composition are non-spherical; and / or (16) the nanoparticles comprise less than about 2.5% by weight of seco-rapamycin (or between about 0.2% and about 2.5% by weight, as otherwise provided herein) relative to the sum of seco-rapamycin and rapamycin. In some embodiments, the nanoparticle composition can be a nanoparticle suspension, and in some embodiments, the concentration of albumin in the nanoparticle suspension in the nanoparticles is about 1.8 mg / mL to about 3 mg / mL (or as otherwise provided herein).

[0143] In some embodiments, the non-nanoparticle portion of the composition, or the non-nanoparticle portion of a commercial batch of the composition, has one or more of the following defining characteristics: (1) about 80% to about 95% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin monomer; (2) about 5% to about 14% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin dimer; and / or (3) about 1% to about 5% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin polymer (or albumin trimer). In some embodiments, the nanoparticle composition may be a nanoparticle suspension, and the non-nanoparticle portion of the nanoparticle suspension may have one or more of the following defining characteristics (in addition to, or instead of, any one of the preceding defining characteristics): (1) the concentration of albumin in the non-nanoparticle portion of the composition is from about 30 mg / mL to about 100 mg / mL (or as otherwise provided herein); and / or (2) the concentration of rapamycin in the non-nanoparticle portion is from about 20 μg / mL to about 55 μg / mL (or as otherwise provided herein).

[0144] In some embodiments, the non-nanoparticle portion of the composition, or the non-nanoparticle portion of a commercial batch of the composition, has one or more of the following defining characteristics: (1) about 80% to about 95% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin monomer; (2) about 4% to about 14% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin dimer; and / or (3) about 0.5% to about 4% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of oligomer; (4) about 0.5% to about 3% (or as otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin polymer (other than albumin oligomer). In some embodiments, the nanoparticle composition may be a nanoparticle suspension, and the non-nanoparticle portion of the nanoparticle suspension may have one or more of the following defining characteristics (in addition to, or instead of, any one of the preceding defining characteristics): (1) the concentration of albumin in the non-nanoparticle portion of the composition is between about 30 mg / mL and about 100 mg / mL (or as otherwise provided herein); and / or (2) the concentration of rapamycin in the non-nanoparticle portion is between about 20 μg / mL and about 55 μg / mL (or as otherwise provided herein).

[0145] The compositions (e.g., pharmaceutical compositions), or commercial batches of compositions (e.g., pharmaceutical compositions) described herein, can be in liquid (e.g., as nanoparticle suspensions) or powder form. For example, in some embodiments, the compositions are liquid nanoparticle suspensions (e.g., before lyophilization). In some embodiments, the compositions are reconstituted suspensions (e.g., in an aqueous solution such as a saline solution). In some embodiments, the compositions are dried, e.g., lyophilized. Lyophilized compositions are typically white or slightly yellow lyophilized cakes that can be crushed into a loose powder and / or reconstituted into an aqueous suspension. In some embodiments, the compositions are sterile. In some embodiments, the compositions are contained in a sealed container, such as a sealed vial (e.g., a glass vial) or a sealed bag.

[0146] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin) and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0147] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin) and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0148] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0149] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0150] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0151] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0152] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0153] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0154] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0155] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 42% to about 62% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension.In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or a sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0156] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0157] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0158] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0159] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin. In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0160] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0161] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0162] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0163] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable for at least 24 hours at 4° C. and / or 25° C. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0164] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0165] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0166] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) comprising rapamycin and albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0167] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0168] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0169] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin), and a core comprising rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg, a viscosity of about 1.2 cP to about 1.5 cP, and a pH of about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0170] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), comprising about 55% (by weight) to about 65% (by weight) rapamycin and about 25% (by weight) to about 45% (by weight) albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension.In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0171] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), comprising about 55% (by weight) to about 65% (by weight) rapamycin and about 25% (by weight) to about 45% (by weight) albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0172] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin, and the albumin constitutes about 25% to about 45% by weight of the nanoparticles, and the rapamycin constitutes about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable for at least 24 hours at 4° C. and / or 25° C. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0173] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); albumin comprises about 25% to about 45% by weight of the nanoparticles, and rapamycin comprises about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP.In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0174] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), comprising about 55% (by weight) to about 75% (by weight) of rapamycin and about 25% (by weight) to about 45% (by weight) of albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0175] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; (c) a non-nanoparticle portion comprising albumin (e.g., human albumin); and (d) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 7% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg.In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0176] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin), the albumin constitutes about 25% to about 45% by weight of the nanoparticles, and the rapamycin constitutes about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg, a viscosity of about 1.2 cP to about 1.5 cP, and a pH of about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0177] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin), or ... by weight of the albumin. (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; (c) a nanoparticle having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein the rapamycin constitutes about 45% by weight of the nanoparticles and about 55% by weight to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL.In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0178] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 55% to about 75% (by weight) of rapamycin and about 25% (by weight) of rapamycin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin). (b) nanoparticles comprising (a) to (b) about 45% (by weight) of albumin (e.g., human albumin), the nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin, the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 5% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0179] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin; about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin; about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); about 55% to about 75% (by weight) of the albumin in the nanoparticles is in the form of dimeric albumin; about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin; about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; (c) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (d) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 7% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL.In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0180] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin; about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin; about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); albumin comprises about 25% to about 45% by weight of the nanoparticles; and rapamycin comprises about 55% to about 75% by weight of the nanoparticles. (b) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, the coating comprising albumin (e.g., human albumin), constituting 5% by weight of the nanoparticle composition, and having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 5% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0181] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 25% to about 45% by weight of the nanoparticles, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); (b) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV, the nanoparticles comprising a coating containing albumin (e.g., human albumin) and a core containing rapamycin, wherein rapamycin constitutes about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 0.5% to about 7% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 1% to about 4.5% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL.In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0182] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 55% (by weight) to about 75% (by weight) rapamycin and about 25% (by weight) to about 45% (by weight) albumin, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin). (b) nanoparticles comprising albumin (e.g., human albumin) and rapamycin, the nanoparticle composition having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and about 3% or less of the rapamycin in the nanoparticle composition is free rapamycin. In some embodiments, about 0.5% to about 5% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0183] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 55% (by weight) to about 75% (by weight) rapamycin and about 25% (by weight) rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin). (b) a non-nanoparticle portion comprising albumin (e.g., human albumin), the nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (c) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and about 3% or less of the rapamycin in the nanoparticle composition is free rapamycin. In some embodiments, about 0.5% to about 7% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL.In some embodiments, the composition has an osmolality of about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0184] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) albumin (hybrid albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin), albumin comprises about 25% to about 45% by weight of the nanoparticles, and rapamycin comprises about 55% to about 75% by weight of the nanoparticles. (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; (c) a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin; and (d) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and about 3% or less of the rapamycin in the nanoparticle composition is free rapamycin. In some embodiments, about 0.5% to about 5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP.In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0185] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin; about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin; about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); albumin comprises about 25% to about 45% by weight of the nanoparticles; and rapamycin comprises about 55% by weight of the nanoparticles. (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin, the coating comprising albumin and the core comprising rapamycin, the coating comprising albumin and the core comprising rapamycin, and the nanoparticle composition has a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (c) a non-nanoparticle portion comprising albumin and rapamycin, the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL), and about 3% or less of the rapamycin in the nanoparticle composition is free rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 1% to about 4.5% of the albumin or total albumin in the non-particle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles.In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0186] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 55% (by weight) to about 75% (by weight) rapamycin and about 25% (by weight) to about 45% (by weight) albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin). (b) nanoparticles having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and the total amount of seco-rapamycin and rapamycin in the nanoparticles is less than 3 wt% (e.g., about 0.2 wt% to about 3 wt%). In some embodiments, about 0.5% to about 5% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP.In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0187] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 55% (by weight) to about 75% (by weight) rapamycin and about 25% (by weight) to about 45% (by weight) rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin). (b) nanoparticles comprising (a) albumin (e.g., human albumin) having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and the sum of seco-rapamycin and rapamycin in the nanoparticles is less than 3 wt% (e.g., about 0.2 wt% to about 3 wt%) seco-rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 1% to about 4.5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles.In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0188] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) a coating comprising albumin (e.g., human albumin), wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin), the albumin comprises about 25% to about 45% by weight of the nanoparticles, and the rapamycin comprises about 55% to about 75% by weight of the nanoparticles. (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; (c) a non-nanoparticle portion comprising albumin (e.g., human albumin); (d) a non-nanoparticle portion comprising albumin (e.g., human albumin); (e.g., human albumin); (e.g., human albumin); (f) a non-nanoparticle portion comprising albumin (e.g., human albumin); (g ... In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg.In some embodiments, the composition has a viscosity of about 1.2 cP to about 1.5 cP. In some embodiments, the composition has a pH of about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0189] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin; about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin; and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); albumin comprises about 25% to about 45% by weight of the nanoparticles; and rapamycin comprises about 55% to about 75% by weight of the nanoparticles; (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and a core comprising rapamycin; (c) a nanoparticle composition having a Z-average particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; (d) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL); and the total amount of seco-rapamycin and rapamycin in the nanoparticles is less than 3% by weight (e.g., about 0.2% to about 3% by weight). In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 1:1 to about 10:1. In some embodiments, about 90% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 90% or more of the rapamycin in the composition is in the nanoparticles.In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.2 cP to about 1.5 cP. In some embodiments, the pH of the composition is about 6.0 to about 7.5. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0190] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0191] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 4% to about 15% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0192] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0193] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 1% to about 4.5% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 14% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 4% to about 15% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0194] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0195] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0196] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0197] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0198] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition.In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0199] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles has an amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension.In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0200] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising rapamycin and albumin (e.g., human albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0201] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0202] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising rapamycin and albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension.In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0203] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the composition has an osmolality of about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0204] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, the nanoparticles comprising a coating comprising albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable for at least 24 hours at 4° C. and / or 25° C. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0205] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin) and having a zeta potential of about -33 mV to about -39 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion or the total albumin in the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0206] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a zeta potential of about -33 mV to about -39 mV, the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained within a sealed container, such as a sealed vial or bag.In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0207] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a zeta potential of about -33 mV to about -39 mV, comprising rapamycin and albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension.In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0208] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a zeta potential of about -33 mV to about -39 mV, comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the composition has an osmolality of about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the composition has a viscosity of about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0209] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a zeta potential of about -33 mV to about -39 mV, the nanoparticles comprising a coating comprising albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable for at least 24 hours at 4° C. and / or 25° C. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0210] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), having a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion or total albumin in the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0211] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV, the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration.In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0212] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV, comprising rapamycin and albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the composition has a pH of about 6.7 to about 6.8. In some embodiments, the composition is stable for at least 24 hours at 4° C. and / or 25° C. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0213] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles comprising rapamycin and albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); the nanoparticles have a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the composition has an osmolality of about 325 mOsm / kg to about 340 mOsm / kg, a viscosity of about 1.3 cP to about 1.35 cP, and a pH of about 6.7 to about 6.8.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0214] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV, the nanoparticles comprising a coating comprising albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and a core comprising rapamycin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0215] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising about 62% to about 68% by weight of rapamycin and about 32% to about 38% by weight of albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form.In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0216] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising about 62% (by weight) to about 68% (by weight) rapamycin and about 32% (by weight) to about 38% (by weight) albumin (e.g., human albumin), wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 0.5% to about 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (other than oligomeric albumin). In some embodiments, about 0.3% to about 4% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of oligomeric albumin. In some embodiments, about 4% to about 15% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 80% to about 95% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0217] In some embodiments, a nanoparticle composition, or a commercial batch of nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric (or trimeric) albumin, and the albumin constitutes about 32% to about 38% by weight of the nanoparticles, and the rapamycin constitutes about 62% to about 68% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric (or trimeric) albumin. In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the non-nanoparticle portion of the nanoparticle composition or the concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours.In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0218] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, comprising about 62% (by weight) to about 68% (by weight) rapamycin and about 32% (by weight) to about 38% (by weight) albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0219] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm, the nanoparticles comprising a coating comprising albumin (e.g., human albumin) and a core comprising rapamycin, wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); albumin constitutes about 32% to about 38% by weight of the nanoparticles; and rapamycin constitutes about 62% to about 68% by weight of the nanoparticles; and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP.In some embodiments, the pH of the composition is about 6.7 to about 6.8. In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterilized, for example, by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition contains less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0220] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises: (a) nanoparticles having a Z-average particle size of about 85 nm to about 95 nm and a zeta potential of about -33 mV to about -39 mV, comprising about 62% (by weight) to about 68% (by weight) rapamycin and about 32% (by weight) to about 38% (by weight) albumin (e.g., human albumin), wherein about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion comprising albumin (e.g., human albumin) and rapamycin; wherein the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (e.g., about 1 mg / mL to about 15 mg / mL). In some embodiments, about 1.5% to about 3% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymeric albumin (or trimeric albumin). In some embodiments, about 7% to about 11% of the albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimeric albumin. In some embodiments, about 83% to about 92% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of monomeric albumin. In some embodiments, the weight ratio of albumin to rapamycin in the composition is about 7:1 to about 9:1. In some embodiments, about 95% or more of the albumin in the composition is in the non-nanoparticle portion. In some embodiments, about 98% to about 99.5% of the rapamycin in the composition is in the nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition in the non-nanoparticle portion or the total albumin concentration in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the osmolality of the composition is about 325 mOsm / kg to about 340 mOsm / kg. In some embodiments, the viscosity of the composition is about 1.3 cP to about 1.35 cP. In some embodiments, the pH of the composition is about 6.7 to about 6.8.In some embodiments, the composition is stable at 4°C and / or 25°C for at least 24 hours. In some embodiments, the rapamycin in the nanoparticles is in amorphous form. In some embodiments, the nanoparticle composition is a nanoparticle suspension. In some embodiments, the nanoparticle composition is a dry composition. In some embodiments, the nanoparticle composition is sterile, e.g., by filtration. In some embodiments, the nanoparticle composition is contained in a sealed container, such as a sealed vial or sealed bag. In some embodiments, the nanoparticle composition comprises less than 10 μg / mL of tert-butanol and / or less than 5 μg / mL of chloroform.

[0221] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin, about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, and about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin (other than oligomeric albumin), such as about 62% (heavy albumin). (b) nanoparticles comprising (a) about 85 nm to about 95 nm Z-average particle size and about -33 mV to about -39 mV, the nanoparticles comprising about 68% (by weight) rapamycin an...

Claims

1. 1. A nanoparticle composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a non-nanoparticle portion comprising albumin and rapamycin, A nanoparticle composition, wherein about 80% to about 95% of the albumin in the composition is in the form of monomeric albumin, about 4% to about 15% of the albumin in the composition is in the form of dimeric albumin, and about 0.5% to about 5% of the albumin in the composition is in the form of polymeric albumin, when the percentage of albumin in the composition that is in the form of monomeric albumin, dimeric albumin, or polymeric albumin is measured by subjecting the composition to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector.

2. 2. The nanoparticle composition of claim 1, wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, dimeric albumin, or polymeric albumin, as determined by separating the nanoparticles from non-nanoparticle portions, resuspending the nanoparticles in saline, and subjecting the resuspended nanoparticles to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector; wherein about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles is in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin.

3. 3. The nanoparticle composition of claim 1 or 2, wherein the proportion of albumin in the non-nanoparticle portion that is in the form of monomeric albumin, dimeric albumin, or polymeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector, and wherein about 80% to about 95% of the albumin in the non-nanoparticle portion is in the form of monomeric albumin, about 4% to about 14% of the albumin in the non-nanoparticle portion is in the form of dimeric albumin, and about 0.5% to about 5% of the albumin in the non-nanoparticle portion is in the form of polymeric albumin.

4. 1. A nanoparticle composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a non-nanoparticle portion comprising albumin and rapamycin, A nanoparticle composition, wherein about 42% to about 60% of the albumin in the nanoparticles is in the form of polymeric albumin other than oligomeric albumin, as determined by separating the nanoparticles from non-nanoparticle portions, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography.

5. 5. The nanoparticle composition of claim 4, wherein about 1% to about 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin, as determined by separating the nanoparticles from non-nanoparticle portions, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography.

6. 6. The nanoparticle composition of claim 4 or 5, wherein the percentage of albumin in the nanoparticles that is in the form of monomeric or dimeric albumin is determined by separating the nanoparticles from non-nanoparticle portions, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, wherein about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, or about 5% to about 16% of the albumin in the nanoparticles is in the form of dimeric albumin.

7. 7. The nanoparticle composition of any one of claims 4 to 6, wherein the proportion of albumin in the non-nanoparticle portion that is in the form of monomeric albumin, dimeric albumin, oligomeric albumin, and / or polymeric albumin other than oligomeric albumin is determined by separating the nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography, wherein about 80% to about 95% of the albumin in the non-nanoparticle portion is in the form of monomeric albumin, about 4% to about 14% of the albumin in the non-nanoparticle portion is in the form of dimeric albumin, about 0.5% to about 4% of the albumin in the non-nanoparticle portion is in the form of oligomeric albumin, and / or about 0.5% to about 3% of the albumin in the non-nanoparticle portion is in the form of polymeric albumin other than oligomeric albumin.

8. 8. The nanoparticle composition of claim 4, wherein the proportion of monomeric albumin, dimeric albumin, oligomeric albumin, and / or polymeric albumin other than oligomeric albumin in the composition is measured by subjecting the composition to size exclusion chromatography, and the proportion of monomeric albumin, dimeric albumin, oligomeric albumin, and / or polymeric albumin other than oligomeric albumin in the composition is about 80% to about 95% of the total albumin in the composition is in the form of monomeric albumin, about 4% to about 15% of the total albumin in the composition is in the form of dimeric albumin, about 0.3% to about 3% of the total albumin in the composition is in the form of oligomeric albumin, and / or about 2% to about 7% of the total albumin in the composition is in the form of polymeric albumin other than oligomeric albumin.

9. The nanoparticle composition of any one of claims 1 to 8, wherein the seco-rapamycin is from about 0.2% to about 3% by weight of the total of seco-rapamycin and rapamycin in the composition.

10. 1. A nanoparticle composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a non-nanoparticle portion comprising albumin and rapamycin, wherein the seco-rapamycin is less than 3% by weight of the combined seco-rapamycin and rapamycin in the composition.

11. The nanoparticle composition of any one of claims 1 to 10, wherein less than 1% of the rapamycin in the composition is free rapamycin.

12. A nanoparticle composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a non-nanoparticle portion comprising albumin and rapamycin, wherein less than 1% of the rapamycin in the composition is free rapamycin.

13. The nanoparticle composition of any one of claims 1 to 12, wherein the volume-weighted mean particle size of the nanoparticles is about 200 nm or less, or about 150 nm or less.

14. The nanoparticle composition of any one of claims 1 to 13, wherein the nanoparticles have a Z-average particle size of about 200 nm or less, or about 150 nm or less.

15. The nanoparticle composition of any one of claims 1 to 14, wherein the nanoparticles have a polydispersity index of less than 0.

3.

16. The range of particle size distribution of nanoparticles ((D ｖ 95-D ｖ 5) / D ｖ 16. The nanoparticle composition of any one of claims 1 to 15, wherein 50) is from about 0.8 to about 1.

2.

17. 17. The nanoparticle composition of any one of claims 1 to 16, wherein the nanoparticles are about 25% to about 45% by weight albumin.

18. 18. The nanoparticle composition of any one of claims 1 to 17, wherein the nanoparticles are about 55% to about 75% rapamycin by weight.

19. 19. The nanoparticle composition of any one of claims 1 to 18, wherein the weight ratio of albumin to rapamycin in the composition is from about 1:1 to about 10:

1.

20. The nanoparticle composition of any one of claims 1 to 19, wherein the nanoparticle composition is a nanoparticle suspension.

21. 21. The nanoparticle composition of claim 20, wherein the albumin concentration in the composition is from about 1 mg / mL to about 100 mg / mL.

22. 21. The nanoparticle composition of claim 20, wherein the albumin concentration in the composition is from about 30 mg / mL to about 100 mg / mL.

23. The nanoparticle composition of any one of claims 20 to 22, wherein the concentration of rapamycin in the nanoparticle composition is from about 1 mg / mL to about 100 mg / mL.

24. The nanoparticle composition of any one of claims 20 to 22, wherein the concentration of rapamycin in the nanoparticle composition is from about 1 mg / mL to about 50 mg / mL.

25. 25. The nanoparticle composition of any one of claims 20 to 24, wherein the osmolality of the composition is from about 280 mOsm / kg to about 400 mOsm / kg.

26. The nanoparticle composition of any one of claims 20 to 25, wherein the viscosity of the composition is from about 1.2 cP to about 1.5 cP.

27. The nanoparticle composition of any one of claims 20 to 26, wherein the composition is stable at 25°C for at least 24 hours.

28. The nanoparticle composition of any one of claims 20 to 27, wherein the composition is stable at 4°C for at least 24 hours.

29. The nanoparticle composition of any one of claims 20 to 28, wherein the nanoparticles are resuspended from a dry composition.

30. The nanoparticle composition of any one of claims 20 to 29, wherein the pH of the composition is from about 6.0 to about 7.

5.

31. The nanoparticle composition of any one of claims 1 to 30, wherein the composition is a dry composition.

32. The nanoparticle composition of any one of claims 1 to 31, wherein the composition comprises less than 250 ppm of tert-butanol.

33. The nanoparticle composition of any one of claims 1 to 32, wherein the composition comprises less than 60 ppm of chloroform.

34. 34. The nanoparticle composition of any one of claims 1 to 33, wherein the nanoparticles have a zeta potential of about -25 mV to about -50 mV.

35. 35. The nanoparticle composition of any one of claims 1 to 34, wherein the composition has an amorphous morphology as determined by measuring the crystallinity of a lyophilized form of the composition by X-ray diffraction.

36. 36. The nanoparticle composition of any one of claims 1 to 35, wherein the nanoparticles have an amorphous morphology as determined by isolating the nanoparticles from the composition, lyophilizing the isolated nanoparticles, and measuring the crystallinity of the isolated and lyophilized nanoparticles by X-ray diffraction.

37. 37. The nanoparticle composition of any one of claims 1 to 36, wherein the rapamycin in the nanoparticles has an amorphous morphology as determined by Raman spectroscopy, polarized light microscopy, differential scanning calorimetry (DSC), modulated differential scanning calorimetry (mDSC), Fourier transform infrared (FTIR) spectroscopy, or nuclear magnetic resonance (NMR) spectroscopy.

38. The nanoparticle composition of any one of claims 1 to 37, wherein the vinyl chains of the rapamycin in the nanoparticles interact with albumin in the nanoparticles.

39. 39. The nanoparticle composition of any one of claims 1 to 38, wherein at least a portion of the nanoparticles are non-spherical as determined by cryo-transmission electron microscopy (cryo-TEM).

40. 40. The nanoparticle composition of any one of claims 1 to 39, wherein at least 20% of the nanoparticles are non-spherical as determined by cryo-transmission electron microscopy (cryo-TEM).

41. 41. The nanoparticle composition of any one of claims 1 to 40, wherein at least some of the nanoparticles have a non-smooth surface as determined by cryo-transmission electron microscopy (cryo-TEM).

42. 41. The nanoparticle composition of any one of claims 1 to 40, wherein at least 20% of the nanoparticles have a non-smooth surface as determined by cryo-transmission electron microscopy (cryo-TEM).

43. The nanoparticle composition of any one of claims 1 to 42, wherein the albumin is human albumin.

44. At least 90% by weight of the rapamycin in the composition is present in the nanoparticles. A nanoparticle composition according to any one of claims 1 to 43.

45. The nanoparticle composition of any one of claims 1 to 44, wherein the nanoparticle composition is sterile.

46. The nanoparticle composition of any one of claims 1 to 45, wherein the nanoparticle composition comprises a caprylic acid derivative and / or a tryptophan derivative.

47. 47. The nanoparticle composition of any one of claims 1 to 46, wherein the pharmaceutical composition is associated with a unit dosage label indicating the amount of rapamycin in the pharmaceutical composition, and wherein the amount of rapamycin in the pharmaceutical composition is within 10% of the amount of rapamycin indicated on the unit dosage label.

48. The nanoparticle composition of any one of claims 1 to 47, wherein the nanoparticle composition is contained in a sealed container.

49. 49. The nanoparticle composition of claim 48, wherein the sealed container is a sealed vial or a sealed bag.

50. The nanoparticle composition of any one of claims 1 to 49, wherein the nanoparticle composition is a pharmaceutical composition.

51. A commercial batch of the nanoparticle composition of any one of claims 1 to 50.

52. a dispersed organic phase comprising nanodroplets containing rapamycin dissolved in an organic solvent comprising chloroform and tert-butanol; and A continuous aqueous phase containing albumin wherein the batch of emulsion comprises at least 20 grams of rapamycin.

53. 53. The emulsion of claim 52, wherein the organic solvent comprises about 10% to about 50% by volume of tert-butanol.

54. 54. The emulsion of claim 52 or 53, wherein the organic solvent comprises about 50% to about 90% by volume of chloroform.

55. 55. The emulsion of any one of claims 52 to 54, wherein the organic solvent comprises chloroform and tert-butanol in a volume ratio of about 1:1 to about 9:

1.

56. 56. The emulsion of any one of claims 52 to 55, wherein the concentration of rapamycin in the organic phase is from about 20 mg / mL to about 300 mg / mL.

57. 57. The emulsion of any one of claims 52 to 56, wherein the concentration of rapamycin in the emulsion is from about 2 mg / mL to about 50 mg / mL.

58. 58. The emulsion of any one of claims 52 to 57, wherein the albumin concentration in the aqueous phase is from about 10 mg / mL to about 200 mg / mL.

59. 59. The emulsion of any one of claims 52 to 58, wherein the albumin concentration in the emulsion is from about 8 mg / mL to about 200 mg / mL.

60. 59. The emulsion according to any one of claims 52 to 58, wherein the organic phase fraction in the emulsion is from about 1% to about 20%.

61. 61. An emulsion according to any one of claims 52 to 60, wherein the nanodroplets have a Z-average particle size of 200 nm or less.

62. 62. The emulsion of any one of claims 52 to 61, wherein the Z-average particle size of the nanodroplets does not increase by more than 30% after storing the emulsion at 4°C for about 4 hours.

63. 63. The emulsion of any one of claims 52 to 62, wherein the Z-average particle size of the nanodroplets does not increase by more than 30% after storing the emulsion at 4°C for about 24 hours.

64. 64. The emulsion of any one of claims 52 to 63, wherein the albumin is human albumin.

65. 65. A method for preparing a commercial batch of a nanoparticle suspension, the method comprising removing organic solvent from a batch of the emulsion of any one of claims 52 to 64 to prepare the nanoparticle suspension.

66. 66. The method of claim 65, wherein the organic solvent is removed using a wiped film evaporator.

67. 67. The method of claim 66, wherein the organic solvent is removed using a rotary evaporator.

68. 68. The method of any one of claims 65 to 67, further comprising forming an emulsion by homogenizing the organic phase and the aqueous phase.

69. 69. The method of any one of claims 65 to 68, wherein the emulsion is stored at about 2°C to about 8°C before removing the organic solvent.

70. 70. The method of claim 69, wherein the emulsion is stored for about 4 hours or about 24 hours.

71. 1. A method for assessing the suitability of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticulate portion comprising albumin and rapamycin, for medical use in a human individual, comprising: Measuring quality control parameters for the pharmaceutical composition; and 1. A method comprising assessing the suitability of a pharmaceutical composition for medical use in a human individual, wherein a measured quality control parameter that is within a quality control threshold indicates the suitability of the pharmaceutical composition for medical use.

72. 72. The method of claim 71, wherein the quality control parameters for the pharmaceutical composition include the percentage of albumin in the composition that is in the form of polymeric albumin other than oligomeric albumin; and wherein the quality control parameters include the percentage of albumin in the composition that is in the form of monomeric albumin in a range set at about 42% to about 60% monomeric albumin, as measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography.

73. 72. The method of claim 71, wherein the quality control parameters for the pharmaceutical composition include the percentage of albumin in the composition in the form of monomeric albumin, dimeric albumin, and polymeric albumin; and the quality control thresholds include the percentage of albumin in the composition that is in the form of monomeric albumin, dimeric albumin, or polymeric albumin in a range set at about 80% to about 95% monomeric albumin, in a range set at about 4% to about 15%, and in a range set at about 0.5% to about 5% polymeric albumin, as measured by subjecting the composition to size exclusion chromatography (SEC) using a saline mobile phase coupled with a multi-angle light scattering (MALS) detector.

74. 72. The method of claim 71, wherein the quality control parameters for the pharmaceutical composition comprise the weight percent of the sum of sec-rapamycin and rapamycin in the composition that is in the form of seco-rapamycin; and the quality control threshold is set at 3% by weight or less of seco-rapamycin.

75. 72. The method of claim 71, wherein the quality control parameters for the pharmaceutical composition include the percentage of rapamycin in the composition that is free rapamycin; and the quality control threshold is set at 1% or less of rapamycin in the composition.

76. 1. A method for releasing a commercial batch of a pharmaceutical composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a nanoparticle portion comprising albumin and rapamycin, the method comprising: assessing the suitability of the pharmaceutical composition for medical use in human individuals using samples of the commercial batch, wherein the suitability of the pharmaceutical composition is assessed according to the method of any one of claims 71 to 75; and Releasing a commercial batch if the pharmaceutical composition is suitable for medical use.

77. 1. A method of processing a sample of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticulate portion comprising albumin and rapamycin to confirm the sample is suitable for medical use in a human individual, comprising: Obtaining a sample from a commercial batch; and 76. A method comprising assessing the suitability of a pharmaceutical composition for medical use in a human individual using a sample of a commercial batch, wherein the suitability of the pharmaceutical composition is assessed according to the method of any one of claims 71 to 75.

78. 1. A method for preparing a pharmaceutical composition for sale, the pharmaceutical composition comprising: (a) nanoparticles comprising rapamycin and albumin; and (b) a non-nanoparticulate portion comprising albumin and rapamycin, the method comprising: assessing the suitability of a pharmaceutical composition for medical use in a human individual according to a method according to any one of claims 71 to 75; identifying the pharmaceutical composition as suitable for medical use in a human individual; and packaging the pharmaceutical composition for sale.

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