Pharmaceutical composition of albumin and rapamycin

Abstract

The present invention provides compositions (e.g., pharmaceutical compositions) comprising nanoparticles containing albumin and rapamycin, and commercial batches of such compositions. The compositions (e.g., pharmaceutical compositions) have specific physicochemical characteristics and are particularly suitable for use in treating diseases such as cancer. Methods for preparing and using the compositions (e.g., pharmaceutical compositions) are also provided.

Description

[Technical Field]

[0001] (Cross-reference of related appearances) This application claims priority under U.S. Provisional Patent Application No. 62 / 927047, filed on 28 October 2019, and U.S. Provisional Patent Application No. 62 / 936212, filed on 15 November 2019, both of which are incorporated herein by reference for all purposes.

[0002] (Technical field of invention) Compositions containing nanoparticles having albumin and rapamycin, and emulsions containing albumin and rapamycin are described herein. Furthermore, methods for preparing such compositions and emulsions and / or controlling their quality are described herein. [Background technology]

[0003] Mammalian target of rapamycin (mTOR) is a conserved serine / threonine kinase that integrates intracellular and extracellular signals and acts 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 is linked to the increase in several human diseases, including cancer and autoimmune disorders. As a result, mTOR inhibitors have found widespread applications in the treatment of diverse pathological conditions such as solid tumors, hematological malignancies, organ transplantation, restenosis, and rheumatoid arthritis.

[0004] Rapamycin, also known as sirolimus (INN / USAN), is an immunosuppressant used to suppress rejection in organ transplants; it is particularly useful in kidney transplants. Rapamycin-eluting stents are approved in the United States for the treatment of 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 upon the pharmacokinetic and pharmacodynamic properties of rapamycin. For example, temsirolimus is approved in the United States and Europe for the treatment of renal cell carcinoma. Everolimus is approved in the United States for the treatment of advanced breast cancer, pancreatic neuroendocrine neoplasms, advanced renal cell carcinoma, and subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis. Rapamycin works by binding to cytosolic protein FK-binding protein 12 (FKBP12), and then this rapamycin-FKBP12 complex directly binds to mTOR complex 1 (mTORC1), thereby inhibiting the mTOR pathway.

[0005] Albumin-based nanoparticle compositions have been developed as drug delivery systems for delivering substantially water-insoluble drugs. See, for example, U.S. Patents 5,916,596, 6506,405, 6749,868, 6537,579, 7820,788, and 7923,536. Nab-paclitaxel, an albumin-stabilized nanoparticle formulation of paclitaxel marketed under the trade name ABRAXANE®, is approved in the United States and various other countries for the treatment of metastatic breast cancer, pancreatic cancer, and lung cancer. All publications, patents, patent applications, and disclosures of published patent applications referenced herein are thus incorporated herein by reference in their entirety. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] U.S. Patent No. 5916596 [Patent Document 2] U.S. Patent No. 6506405 [Patent Document 3] U.S. Patent No. 6749868 [Patent Document 4] U.S. Patent No. 6537579 [Patent Document 5] U.S. Patent No. 7820788 [Patent Document 6] U.S. Patent No. 7923536 [Overview of the project]

[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 herein. Furthermore, methods for evaluating the suitability of pharmaceutical compositions for use in human organisms, and methods for processing pharmaceutical compositions (and commercial batches of such pharmaceutical compositions) that have been identified as suitable for use in human organisms are also described herein.

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

[0009] The nanoparticle compositions described herein may comprise (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticle portion comprising albumin and rapamycin. In some embodiments, the nanoparticles comprise a core comprising rapamycin and a coating comprising albumin.

[0010] When the proportion of albumin in a nanoparticle composition, or a commercial batch of such a nanoparticle composition, is measured by subjecting the composition to size exclusion chromatography (SEC) using a Saline mobile phase with a multi-angle light scattering (MALS) detector, approximately 80% to 95% of the albumin in the composition is in the form of monomeric albumin, approximately 4% to 15% is in the form of dimeric albumin, and approximately 0.5% to 5% is in the form of polymeric albumin. In the nanoparticle portion of the composition, the proportion of albumin in the nanoparticle portion, whether in the form of monomeric albumin, dimer albumin, or polymeric albumin, is measured by separating the nanoparticles from the non-nanoparticle portion, resuspending the nanoparticles in a Saline, and subjecting the resuspended nanoparticles to size exclusion chromatography (SEC) using a Saline mobile phase with an integrated multi-angle light scattering (MALS) detector. The results show that approximately 70% to 85% of the albumin in the nanoparticle portion is in the form of monomeric albumin, approximately 9% to 20% is in the form of dimer albumin, and approximately 5% to 15% is in the form of polymeric albumin. In the non-nanoparticle portion of the composition, the proportion of albumin in the non-nanoparticle portion, whether in the form of monomeric albumin, dimer 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 integrated with a multi-angle light scattering (MALS) detector. Approximately 80% to 95% of the albumin in the non-nanoparticle portion is in the form of monomeric albumin, approximately 4% to 14% is in the form of dimer albumin, and approximately 0.5% to 5% is in the form of polymeric albumin. The nanoparticle composition may further be 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.

[0011] In another characterization of a nanoparticle composition or a commercial batch of a nanoparticle composition, when the proportion of albumin in the nanoparticle portion that is in the form of polymer albumin other than oligomeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, approximately 42% to 60% of the albumin in the nanoparticle portion is in the form of polymer albumin other than oligomeric albumin. When the proportion of albumin in the nanoparticle portion that is in the form of oligomeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, approximately 1% to 4.5% of the albumin in the nanoparticle portion is in the form of oligomeric albumin. When the proportion of albumin in the nanoparticle portion, whether in the form of monomeric albumin or dimer albumin, is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, it is found that approximately 25% to 50% of the albumin in the nanoparticle portion is in the form of monomeric albumin, or approximately 5% to 16% of the albumin in the nanoparticle portion is in the form of dimer albumin. Regarding the non-nanoparticle portion, the proportion of albumin in the non-nanoparticle portion, which is in the form of monomeric albumin, dimer albumin, oligomeric albumin, and / or polymer albumin other than oligomeric albumin, was measured by separating nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography. The results showed that approximately 80% to 95% of the albumin in the non-nanoparticle portion was in the form of monomeric albumin, approximately 4% to 14% was in the form of dimer albumin, approximately 0.5% to 4% was in the form of oligomeric albumin, and / or approximately 0.5% to 3% was in the form of polymer albumin other than oligomeric albumin.Overall, when the proportions of monomeric albumins, dimer albumins, oligomeric albumins, and / or polymer albumins other than oligomeric albumins in the composition are measured by size exclusion chromatography, approximately 80% to 95% of the total albumins in the composition are in the form of monomeric albumins, approximately 4% to 15% of the total albumins in the composition are in the form of dimer albumins, approximately 0.3% to 3% of the total albumins in the composition are in the form of oligomeric albumins, and / or approximately 2% to 7% of the total albumins in the composition are in the form of polymer albumins other than oligomeric albumins. The nanoparticle composition may further be 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 85% of the albumin in the nanoparticle portion is in the form of monomeric albumin. In some embodiments, about 5% to 15% of the albumin in the nanoparticle portion is in the form of polymeric albumin. In some embodiments, about 9% to 20% of the albumin in the nanoparticle portion is in the form of dimeric albumin. In some embodiments, about 0.5% to 5% of the albumin in the non-nanoparticle portion is in the form of polymeric albumin. In some embodiments, about 80% to 95% of the albumin in the non-nanoparticle portion is in the form of monomeric albumin. In some embodiments, about 4% to 14% of the albumin in the non-nanoparticle portion is in the form of dimeric albumin. In some embodiments, about 0.5% to 5% of the total albumin in the composition is in the form of polymeric albumin. In some embodiments, about 80% to 95% of the total albumin in the composition is in the form of monomeric albumin. In some embodiments, about 4% to 15% of the total albumin in the composition is in the form of dimer albumin. In some embodiments, the proportion of polymer albumin, dimer albumin, or monomer albumin is measured using size exclusion chromatography.

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

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

[0015] In some embodiments of the nanoparticle composition, the weight percentage of albumin in the nanoparticle portion is about 25% to about 45%. In some embodiments, the weight percentage 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 about 1:1 to about 10:1.

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

[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 were resuspended from the 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 within 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 within 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 within the non-nanoparticle portion is about 20 μg / mL to about 55 μg / mL. In some embodiments, the concentration of rapamycin in the composition within the nanoparticle portion is about 1 mg / mL to about 15 mg / mL.

[0020] In some embodiments of the nanoparticle composition, the weight 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.

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

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

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

[0024] In some embodiments of the nanoparticle composition, the composition has an amorphous form, which is determined by measuring the crystallinity of the freeze-dried form of the composition by X-ray diffraction. In some embodiments, the nanoparticles have an amorphous form, which is determined by separating the nanoparticles from the composition, freeze-drying the separated nanoparticles, and measuring the crystallinity of the separated and freeze-dried nanoparticles by X-ray diffraction.

[0025] In some embodiments of the nanoparticle composition, the rapamycin in the nanoparticles has an amorphous form 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 chain of rapamycin in the nanoparticle portion interacts with albumin in the nanoparticle.

[0027] In some embodiments of the nanoparticle composition, at least a portion of the nanoparticles are non-spherical. In 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 contains less than about 3% by weight of seco-rapamycin in the nanoparticles, compared to the total amount of seco-rapamycin and rapamycin in the nanoparticles. In some embodiments, the nanoparticle composition contains more than about 0.2% by weight of seco-rapamycin in the nanoparticles, compared to the total amount of seco-rapamycin and rapamycin in the nanoparticles.

[0029] In some embodiments of the nanoparticle composition, about 3% or less 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] Emulsions (e.g., commercial batch emulsions) comprising a dispersed organic phase containing nanodroplets of rapamycin dissolved in an organic solvent containing chloroform and tert-butanol, and a continuous aqueous phase containing albumin are also described herein.

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

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

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

[0039] In some embodiments of the emulsion, the nanodroplets have a Z-average particle size of approximately 200 nm or less. In some embodiments, the nanodroplets have a Z-average particle size of approximately 50 nm to approximately 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 the emulsion is stored 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. These methods may involve removing the organic solvent from an emulsion comprising a dispersed organic phase containing nanodroplets of rapamycin dissolved in an organic solvent containing chloroform and tert-butanol, and a continuous aqueous phase containing albumin. In some embodiments, the organic solvent is removed using a wiped-film evaporator or a rotary evaporator. The evaporator may be a continuous evaporator or a batch evaporator. A continuous evaporator is one in which the feed and product flows are continuous and their concentrations generally remain constant due to consistent input to the feed flow. A batch evaporator is one in which the feed and product flows 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 the nanoparticle suspension, the organic solvent contains about 10% to about 50% by volume of tert-butanol. In some embodiments, the organic solvent contains about 50% to about 90% by volume of chloroform. In some embodiments, the organic solvent contains 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 phase fraction of the organic phase 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 approximately 50 nm to approximately 200 nm. In some embodiments, the albumin is human albumin.

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

[0045] In some embodiments for preparing a nanoparticle suspension, the method further includes filtering the organic phase, the aqueous phase, or both before forming an emulsion.

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

[0047] In some embodiments of preparing a nanoparticle suspension, the method further includes adding an albumin-containing solution to the nanoparticle suspension. In some embodiments, the addition of the albumin-containing solution adjusts the weight ratio of albumin to rapamycin in the nanoparticle suspension to between approximately 1:1 and approximately 10:1.

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

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

[0050] A method for evaluating the suitability of a pharmaceutical composition for medical use in a human organism, comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticle portion comprising albumin and rapamycin, comprising measuring quality control parameters for the pharmaceutical composition and evaluating the suitability of the pharmaceutical composition for medical use in a human organism, wherein the measured quality control parameters being within a quality control threshold indicates suitability of the pharmaceutical composition for medical use. In some embodiments, the method further comprises separating nanoparticles from the non-nanoparticle portion, and the quality control parameters include quality control parameters for the nanoparticles or the non-nanoparticle portion. In some embodiments, the nanoparticles comprise a core comprising rapamycin and a coating comprising albumin. The quality control parameters may be any or a combination of several parameters described herein for the nanoparticle composition, which are evaluated, for example, by the corresponding method described herein.

[0051] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of total albumin in the nanoparticle portion and albumin in monomeric albumin form in the nanoparticle portion; a weight percentage of about 70% to about 85% of total albumin in the nanoparticle portion indicates suitability for medical use of the pharmaceutical composition.

[0052] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of polymer albumin in the nanoparticle portion relative to the total albumin in the nanoparticle portion; a weight percentage of albumin in the form of polymer albumin in the nanoparticle portion relative to the total albumin in the nanoparticle portion of the nanoparticle portion of about 5% to about 15% indicates suitability of the pharmaceutical composition for medical use.

[0053] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of dimer albumin in the nanoparticle portion relative to the total albumin in the nanoparticle portion; a weight percentage of albumin in the form of dimer albumin in the nanoparticle portion relative to 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 evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of polymer albumin in the non-nanoparticle portion of total albumin in the non-nanoparticle portion; a weight percentage of albumin in the form of polymer albumin in the non-nanoparticle portion of 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 evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of monomeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion; a weight percentage of albumin in the form of monomeric albumin in the non-nanoparticle portion of the total albumin in the non-nanoparticle portion of about 80% to about 95% indicates suitability for medical use of the pharmaceutical composition.

[0056] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of dimer albumin in the non-nanoparticle portion of total albumin in the non-nanoparticle portion; a weight percentage of albumin in the form of dimer albumin in the non-nanoparticle portion of 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 evaluating the suitability of a pharmaceutical composition, the quality control parameters include the weight percentage of total albumin in the composition and albumin in the form of polymer albumin in the composition; a weight percentage of total albumin in the composition and albumin in the form of polymer albumin in the composition of about 0.5% to about 5% indicates suitability of the pharmaceutical composition for medical use.

[0058] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of total albumin in the composition and albumin in monomeric albumin form; a weight percentage of total albumin in the composition and albumin in monomeric albumin form being about 80% to about 95% indicates suitability of the pharmaceutical composition for medical use.

[0059] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the form of dimer albumin in the composition relative to the total albumin in the composition; a weight percentage of albumin in the form of dimer albumin in the composition relative to the total albumin in the composition of about 4% to about 15% indicates suitability of the pharmaceutical composition for medical use.

[0060] In some embodiments for evaluating the suitability of a pharmaceutical composition, the proportion of polymer albumin, dimer albumin, or monomer albumin is measured using size exclusion chromatography.

[0061] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the volume-weighted average particle size of nanoparticles; a volume-weighted average particle size of nanoparticles of approximately 200 nm or less indicates suitability for medical use of the pharmaceutical composition.

[0062] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the volume-weighted average particle size of nanoparticles; a volume-weighted average particle size of nanoparticles between approximately 50 nm and approximately 200 nm indicates suitability for medical use of the pharmaceutical composition.

[0063] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameters include the Z-mean particle size of the nanoparticles; a Z-mean particle size of approximately 200 nm or less indicates suitability of the pharmaceutical composition for medical use.

[0064] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the Z-mean particle size of the nanoparticles; a Z-mean particle size of approximately 50 nm to approximately 200 nm indicates suitability for medical use of the pharmaceutical composition.

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

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

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

[0068] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of albumin in the nanoparticle portion; a weight percentage of albumin in the nanoparticle portion of about 25% to about 45% indicates suitability of the pharmaceutical composition for medical use.

[0069] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of rapamycin in the nanoparticle portion; a weight percentage of approximately 55% to approximately 75% of rapamycin in the nanoparticle portion indicates suitability for medical use of the pharmaceutical composition.

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

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

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

[0073] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the proportion of rapamycin in the nanoparticle portion of the composition; a proportion of rapamycin in the nanoparticle portion of the composition of about 98% or more indicates suitability of the pharmaceutical composition for medical use.

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

[0075] In some embodiments for evaluating 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 evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the concentration of albumin in the composition; an albumin concentration of approximately 30 mg / mL to approximately 100 mg / mL indicates suitability of the pharmaceutical composition for medical use.

[0077] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the concentration of albumin in the non-nanoparticle portion of the composition; a concentration of albumin in the non-nanoparticle portion of the composition between approximately 30 mg / mL and approximately 100 mg / mL indicates suitability of the pharmaceutical composition for medical use.

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

[0079] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes 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 suitability of the pharmaceutical composition for medical use.

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

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

[0082] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the weight osmolality of the composition; a weight osmolality of approximately 300 mOSm / kg to approximately 350 mOSm / kg indicates suitability for medical use of the pharmaceutical composition.

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

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

[0085] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the stability of the composition; the composition being stable at 4°C for at least 24 hours indicates suitability for medical use.

[0086] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the pH of the composition; a pH of approximately 6.0 to approximately 7.5 indicates suitability of the pharmaceutical composition for medical use.

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

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

[0089] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameters include the zeta potential of the nanoparticles; a zeta potential of approximately -25mV to approximately -50mV indicates suitability of the pharmaceutical composition for medical use.

[0090] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the morphology of the composition, which is measured by measuring the degree of crystallinity of the lyophilized form of the composition by X-ray diffraction; and the amorphous form of the composition indicates the suitability of the pharmaceutical composition for medical use.

[0091] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the morphology of the composition, which is measured by separating nanoparticles from the composition, freeze-drying the separated nanoparticles, and measuring the crystallinity of the separated and freeze-dried nanoparticles by X-ray diffraction; the amorphous morphology of the composition indicates the suitability of the pharmaceutical composition for medical use.

[0092] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the morphology of the composition, which 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; the amorphous morphology of the composition indicates the suitability of the pharmaceutical composition for medical use.

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

[0094] In some embodiments for evaluating the suitability of a pharmaceutical composition, quality control parameters include the proportion of non-spherical nanoparticles; the 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 evaluating the suitability of a pharmaceutical composition, quality control parameters include the percentage of non-spherical nanoparticles; the identification of at least 20% of nanoparticles as non-spherical indicates suitability of the pharmaceutical composition for medical use.

[0096] In some embodiments for evaluating the suitability of a pharmaceutical composition, the quality control parameter includes the weight percentage of seco-rapamycin compared to the total of seco-rapamycin in the nanoparticle portion and rapamycin; a seco-rapamycin content of less than 2.5% compared to the total of seco-rapamycin in the nanoparticle portion indicates suitability for medical use of the pharmaceutical composition.

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

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

[0099] A method for launching a commercial batch of a pharmaceutical composition comprising (a) nanoparticles comprising rapamycin and albumin, and (b) a non-nanoparticle 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 organism, and launching the commercial batch if the pharmaceutical composition is suitable for medical use.

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

[0101] Also described is a method for preparing a pharmaceutical composition for market release comprising (a) nanoparticles containing rapamycin and albumin, and (b) a non-nanoparticle portion containing albumin and rapamycin, the method comprising: evaluating the suitability of the pharmaceutical composition for medical use in a human organism; identifying the pharmaceutical composition as suitable for medical use in a human organism; and packaging the pharmaceutical composition for market release. In some embodiments, packaging the pharmaceutical composition includes freeze-drying the pharmaceutical composition. In some embodiments, packaging the pharmaceutical composition includes filling the pharmaceutical composition into a container. In some embodiments, the method includes sealing the container. [Brief explanation of the drawing]

[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 (down arrow), spherical particles with uniform density (upper left arrow), and small circular particles (upper right arrow) were observed.

[0104] [Figure 3] Figure 3 shows a Cryo-TEM image of Lot #1 at 21,000x magnification, in which irregularly shaped particles with non-uniform internal density (up arrow), spherical particles with uniform density (down arrow), and small circular particles (center arrow) were observed.

[0105] [Figure 4]Figure 4 shows a representative chromatogram of a pharmaceutical composition containing rapamycin and albumin (Lot #1 after 12 months of storage at 5°C) measured by size exclusion chromatography (SEC). Peaks corresponding to monomers, dimers, polymers, and oligomers (which can be identified by preferred techniques, 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 reconfigured suspension of a pharmaceutical composition containing nanoparticles of rapamycin and albumin. When the suspension was diluted to a concentration below the solubility of rapamycin, the nanoparticles completely disintegrated and dissolved (see the 7-8 data points on the left of 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 the 4-5 data points on the right of 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% Seiline solution).

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

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

[0109] [Figure 8]Figure 8 shows the solubility profiles of a reconfigured suspension of a pharmaceutical composition (Lot #4) containing nanoparticles of rapamycin and albumin at rapamycin concentrations 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. Peaks labeled "polymer" correspond to albumin polymers other than oligomers.

[0111] [Figure 10] Figure 10 shows the SEC-UV chromatogram of the oligomeric profile of the non-nanoparticle portion of human albumin in rapamycin nanoparticle pharmaceuticals. Peaks labeled "polymer" correspond to albumin polymers other than oligomers.

[0112] [Figure 11] Figure 11 shows the SEC-UV chromatogram of the oligomeric profile of the nanoparticle portion of human albumin in rapamycin nanoparticle pharmaceuticals. Peaks labeled "polymer" correspond to albumin polymers other than oligomers. [Modes for carrying out the invention]

[0113] This specification describes nanoparticle compositions (such as pharmaceutical compositions) containing albumin and rapamycin, or commercial batches of nanoparticle compositions. The nanoparticles contain albumin and rapamycin associated with each other within the nanoparticles. For example, the nanoparticles may include a coating containing albumin and a core containing rapamycin. The composition may further include a non-nanoparticle portion containing albumin and rapamycin not contained within the nanoparticle portion. That is, the composition may include 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] Stable emulsions comprising organic phase nanodroplets containing an organic solvent and rapamycin dispersed in a continuous aqueous phase containing albumin are further described herein. The emulsions may be used to produce nanoparticle compositions by removing the organic solvent from the emulsion, for example, according to the production methods described herein.

[0115] Furthermore, quality control processes for pharmaceutical formulations that may be used to ensure that the pharmaceutical composition is suitable for medical use in human organisms are described herein. For example, a pharmaceutical composition may be subjected to a quality control process before a commercial batch of the pharmaceutical composition is launched, which helps to ensure the safety and efficacy of the pharmaceutical composition. This process may include measuring quality control parameters of the composition (i.e., distinct characteristics of the composition that indicate its suitability for medical use) and comparing the measured quality control parameters with quality control thresholds. If the measured parameters are within the thresholds, this comparison indicates that the pharmaceutical composition is suitable for medical use in human organisms.

[0116] The nanoparticle compositions (such as pharmaceutical compositions) described herein, or commercial batches of nanoparticle compositions (such as pharmaceutical compositions), may have distinct features of one or more (any combination) of the following: (1) the oligomeric state of albumin associated with nanoparticles (such as in) the albumin monomer, dimer, oligomer, and / or polymer (or polymer other than oligomer) of albumin associated with nanoparticles (such as in) the albumin monomer; (2) the albumin mono associated with the non-nanoparticle portion of the composition (such as in) the albumin monomer (3) The oligomeric state of albumin associated with (e.g., within) the non-nanoparticle portion of the composition, such as the proportion of albumin monomers, dimers, oligomers, and / or polymers (or non-oligomeric polymers) of the total albumin in the composition; (4) The particle size profile of the nanoparticles, such as the average particle size, polydispersity index, and / or particle size distribution; (5) The proportion of nanoparticles that are albumin (e.g., heavy (6) the proportion of nanoparticles that are %) and / or rapamycin (e.g., %) by weight; (7) the weight ratio of albumin in nanoparticles to rapamycin; (8) the weight ratio of albumin in the non-nanoparticle portion of the composition to rapamycin; (9) the weight ratio of total albumin in the composition to total rapamycin; (10) the proportion of rapamycin in nanoparticles (or the non-nanoparticle portion of the composition) compared to total rapamycin in the composition (e.g., %) by weight; (11) the proportion of total albumin in the composition (12) The percentage (e.g., by weight) of albumin in the non-nanoparticle portion (or in the nanoparticles) compared to (13) the concentration of albumin in 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 weight osmolality of the composition; (19) The viscosity of the composition; (20) The pH of the composition;(21) Stability of nanoparticles in the composition; (22) Amount of residual solvent in the composition; (23) Zeta potential of nanoparticles in the composition; (24) Crystalline state of rapamycin in nanoparticles; (25) Particle morphology of nanoparticles such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) Weight % of seco-rapamycin in nanoparticles compared to the total of seco-rapamycin and rapamycin by weight; (27) Presence, proportion, or concentration of albumin stabilizers (caprylic acid derivatives, e.g., sodium caprylate and / or tryptophan derivatives, e.g., N-acetyltryptophanate) in the composition; (28) Recovery rate of rapamycin after filtration; (29) In vitro release kinetics of nanoparticles; and / or (30) Proportion of total rapamycin in the composition that is present in the non-nanoparticle portion of the composition and is not bound to albumin. The physicochemical parameters discussed above affect the drug release and delivery of albumin-based rapamycin nanoparticle compositions (such as pharmaceutical compositions), and thus may constitute properties specific to the composition.

[0117] The nanoparticle compositions (such as pharmaceutical compositions) described herein, or commercial batches of nanoparticle compositions (such as pharmaceutical compositions), may have distinct features of one or more (any combination) of the following: (1) the oligomeric state of albumin associated with nanoparticles, such as the proportion of albumin monomers, dimers, and / or polymers (such as trimers) of albumin associated with nanoparticles (e.g., in them); (2) the albumin monomers, dimers, and / or polymers (e.g., trimers) of albumin associated with the non-nanoparticle portion of the composition. (3) The oligomeric state of albumin associated with (e.g., within) the non-nanoparticle portion of the composition, such as the proportion of albumin monomers, dimers, and / or trimers of the total albumin in the composition; (4) The particle size profile of the nanoparticles, such as the average particle size, polydispersity index, and / or particle size distribution; (5) The proportion of nanoparticles that are albumin (e.g., wt%) and / or nanoparticles that are rapamycin (e.g., wt%); (6) The weight ratio of albumin in the nanoparticles to rapamycin; (7) (8) The weight ratio of albumin in the non-nanoparticle portion of the composition to rapamycin; (9) The weight ratio of total albumin in the composition to total rapamycin; (10) The proportion of rapamycin in the nanoparticles (or non-nanoparticle portion of the composition) compared to total rapamycin in the composition (e.g., by weight %); (11) The proportion of albumin in the non-nanoparticle portion (or nanoparticles) compared to total albumin in the composition (e.g., by weight %); (12) The concentration of albumin in the composition; (13) The weight ratio of albumin in the non-nanoparticle portion of the composition (14) Concentration of albumin in the non-particle portion; (15) Concentration of albumin in the composition associated with (e.g., within) the nanoparticles; (16) Concentration of rapamycin in the composition; (17) Concentration of rapamycin in the composition associated with (e.g., within) the nanoparticles; (18) Osmolality by weight of the composition; (19) Viscosity of the composition; (20) 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 rapamycin in the nanoparticles;(25) Particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) Weight % of seco-rapamycin in the nanoparticles compared to the total of seco-rapamycin and rapamycin by weight; (27) Presence, proportion, or concentration of albumin stabilizers in the composition (caprylic acid derivatives, e.g., sodium caprylate and / or tryptophan derivatives, e.g., N-acetyltryptophanate); (28) Recovery rate of rapamycin after filtration; (29) In vitro release kinetics of the nanoparticles; and / or (30) Proportion of total rapamycin in the composition that is present in the non-nanoparticle portion of the composition and is not bound to albumin. The physicochemical parameters discussed above may constitute properties specific to the composition, as they affect the drug release and delivery of albumin-based rapamycin nanoparticle compositions (such as pharmaceutical compositions).

[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 may have distinct features of any one or more (any combination) of the following: (1) the proportion (e.g., by volume %) 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 average particle size, polydispersity index, and / or particle size distribution.

[0119] The compositions (such as pharmaceutical compositions) or commercial batches of nanoparticle compositions (such as pharmaceutical compositions) disclosed herein are useful for treating a variety of diseases, including cancer. Therefore, methods of using such compositions (such as pharmaceutical compositions) to treat diseases, including cancer, are further provided herein. Kits, commercial batches, drugs, and dosage forms containing the compositions (such as pharmaceutical compositions) for use in the methods described herein are also provided.

[0120] Certain exemplary embodiments provided herein disclose pharmaceutical compositions. These are exemplary compositions, and it should be understood that these descriptions apply equally to and describe other compositions of the present invention provided herein, such as compositions having any of the features defined in these exemplary embodiments.

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

[0122] definition As used herein and in the appended claims, the singular “a,” “or,” and “the” refer to multiple subjects unless the context clearly requires otherwise.

[0123] References to values ​​or parameters in this specification include (and should be described) variations in the value or parameter itself. For example, a statement referring to "about X" includes a statement of "X". Furthermore, as used herein, the term "about X to Y" is synonymous with "about X to about Y". Alternatively, the use of "about" preceding any set of numbers includes each "about" in that set of enumerated numbers. For example, a statement referring to "about X, Y, or Z" is intended to describe "about X, about Y, or about Z".

[0124] "Albumin dimer" or "dimer albumin" refers to albumin species that have two or only two albumin units.

[0125] "Albumin monomer" or "monomer albumin" refers to albumin species that have one or only one albumin unit.

[0126] "Albumin polymer" or "polymer albumin" refers to albumin species that have a higher molecular weight than albumin monomers and albumin dimers.

[0127] "Albumin trimer" or "trimmer albumin" refers to albumin species that have three or only three albumin units.

[0128] "Albumin oligomers" refer to low molecular weight polymer albumin species associated with UV absorbance-based size exclusion chromatography peaks observed between peaks associated with albumin dimers and peaks associated with high molecular weight polymer albumin species. Figures 9–11 show exemplary size exclusion chromatograms with labeled peaks for monomers, dimers, oligomers, and polymers (other than oligomers).

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

[0130] Substances described as "in nanoparticles" refer to substances that are part of nanoparticles in any configuration. Therefore, these substances may be coated on the surface of the nanoparticles, located within the core of the nanoparticles, embedded within the nanoparticles, or be a mixture thereof. Substances described as "in the non-nanoparticle portion" of a composition refer to substances in the composition that are not "in nanoparticles."

[0131] The term "individual" refers to, but is not limited to, mammals, including humans, cattle, horses, cats, dogs, rodents, or primates.

[0132] The term "nanoparticles" is used herein to refer to solid particles. The term "nanodroplets" is used to refer to liquid particles, for example, in the context of oil-in-water or other emulsions.

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

[0134] References to relative proportions in a composition are understood to assume that the total percentage of all components in the composition combined equals 100. The relative proportions of one or more components can be adjusted higher or lower so that the combined percentages of the components in the composition equal 100, provided that the proportion of any particular component does not exceed the specified limit for that component.

[0135] Albumin-based nanoparticle composition The nanoparticle compositions described herein, or commercial batches of nanoparticle compositions, comprise (a) nanoparticles comprising rapamycin and albumin, and (b) non-nanoparticle portions comprising rapamycin and albumin. The rapamycin and albumin in 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 portions of the composition, the rapamycin and albumin may or may not be associated with each other (i.e., rapamycin may be in a reversible binding equilibrium with albumin), but they are not associated with each other in a manner that forms nanoparticles. The albumin in the nanoparticles may be further distinguished from the albumin in the non-nanoparticle portions of the composition; for example, the oligomeric profile of albumin in the nanoparticles may differ from the oligomeric profile of albumin in the non-nanoparticle portions of the composition.

[0136] The albumin nanoparticles associate with the rapamycin nanoparticles, so 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 prepared nanoparticles (for example, which may be prepared using the method described herein) can be formulated, filtered, or otherwise processed to obtain a pharmaceutical composition suitable for medical use in human organisms.

[0137] The nanoparticle compositions (such as pharmaceutical compositions) described herein, or commercial batches of nanoparticle compositions (such as pharmaceutical compositions), may have distinct features of one or more (any combination) of the following: (1) the oligomeric state of albumin associated with nanoparticles (such as in) the albumin monomer, dimer, oligomer, and / or polymer (or polymer other than oligomer) of albumin associated with nanoparticles (such as in) the albumin monomer; (2) the albumin mono associated with the non-nanoparticle portion of the composition (such as in) the albumin monomer (3) The oligomeric state of albumin associated with (e.g., within) the non-nanoparticle portion of the composition, such as the proportion of albumin monomers, dimers, oligomers, and / or polymers (or non-oligomeric polymers) of the total albumin in the composition; (4) The particle size profile of the nanoparticles, such as the average particle size, polydispersity index, and / or particle size distribution; (5) The proportion of nanoparticles that are albumin (e.g., heavy (6) the proportion of nanoparticles that are %) and / or rapamycin (e.g., %) by weight; (7) the weight ratio of albumin in nanoparticles to rapamycin; (8) the weight ratio of albumin in the non-nanoparticle portion of the composition to rapamycin; (9) the weight ratio of total albumin in the composition to total rapamycin; (10) the proportion of rapamycin in nanoparticles (or the non-nanoparticle portion of the composition) compared to total rapamycin in the composition (e.g., %) by weight; (11) the proportion of total albumin in the composition (12) The percentage (e.g., by weight) of albumin in the non-nanoparticle portion (or in the nanoparticles) compared to (13) the concentration of albumin in 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 weight osmolality of the composition; (19) The viscosity of the composition; (20) The pH of the composition;(21) Stability of nanoparticles in the composition; (22) Amount of residual solvent in the composition; (23) Zeta potential of nanoparticles in the composition; (24) Crystalline state of rapamycin in nanoparticles; (25) Particle morphology of nanoparticles such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) Weight % of seco-rapamycin in nanoparticles compared to the total of seco-rapamycin and rapamycin by weight; (27) Presence, percentage, or concentration of albumin stabilizers (such as sodium caprylate and / or N-acetyltryptophanate) in the composition; (28) Recovery rate of rapamycin after filtration; (29) In vitro release kinetics of nanoparticles; and / or (30) Percentage of total rapamycin in the composition that is present in the non-nanoparticle portion of the composition and not bound to albumin.

[0138] The nanoparticle compositions (such as pharmaceutical compositions) described herein, or commercial batches of nanoparticle compositions (such as pharmaceutical compositions), may have distinct characteristics of one or more (any combination) of the following: (1) the oligomeric state of albumin associated with nanoparticles (such as in), such as the proportion of albumin monomers, dimers, and / or trimers of albumin associated with nanoparticles (such as in); (2) the proportion of albumin monomers, dimers, and / or trimers of albumin associated with non-nanoparticle portions of the composition (such as in) (3) the oligomeric state of albumin associated with (e.g., within) the non-nanoparticle portion of the composition; (4) the oligomeric state of total albumin in the composition, such as the proportion of albumin monomers, dimers, and / or trimers of total albumin in the composition; (5) the particle size profile of the nanoparticles, such as the average particle size, polydispersity index, and / or particle size distribution; (6) the proportion of nanoparticles that are albumin (e.g., wt%) and / or nanoparticles that are rapamycin (e.g., wt%); (7) the weight ratio of albumin in the nanoparticles to rapamycin; (8) the composition (8) The weight ratio of albumin in the non-nanoparticle portion to rapamycin; (9) The weight ratio of albumin in the non-nanoparticle portion of the composition to rapamycin; (10) The proportion of rapamycin in the nanoparticles (or the non-nanoparticle portion of the composition) compared to the total rapamycin in the composition (e.g., by weight %); (11) The proportion of albumin in the non-nanoparticle portion (or in the nanoparticles) compared to the total albumin in the composition (e.g., by weight %); (12) The concentration of albumin in the composition; (13) The non-nanoparticles of the composition (14) Concentration of albumin in the nanoparticle portion; (15) Concentration of albumin in the composition associated with (e.g., within) the nanoparticles; (16) Concentration of rapamycin in the composition; (17) Concentration of rapamycin in the composition associated with (e.g., within) the nanoparticles; (18) Osmolality by weight of the composition; (19) Viscosity of the composition; (20) 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 rapamycin in the nanoparticles;(25) Particle morphology of the nanoparticles, such as shape, sphericity, coating thickness, and / or surface-to-volume ratio; (26) Weight % of seco-rapamycin in the nanoparticles compared to the total of seco-rapamycin and rapamycin by weight; (27) Presence, proportion, or concentration of albumin stabilizers (caprylic acid derivatives, e.g., sodium caprylate and / or tryptophan derivatives, e.g., N-acetyltryptophanate) in the composition; (28) Recovery rate of rapamycin after filtration; (29) In vitro release kinetics of the nanoparticles; and / or (30) Proportion of total rapamycin in the composition that is present in the non-nanoparticle portion of the composition and is not bound to albumin.

[0139] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, has one or more of the following distinct characteristics: (1) about 80% to about 95% (or further provided herein) of the total albumin in the composition is in the form of monomeric albumin; (2) about 4% to about 15% (or further provided herein) of the total albumin in the composition is in the form of dimer albumin; (3) about 0.5% to about 5% (or further provided herein) of the total albumin in the composition is in the form of polymeric albumin (or trimer albumin); (4) the weight ratio of the total albumin in the composition to the total rapamycin is about 1:1 to about 10:1 (or further provided herein); (5) about 90% or more (or further provided herein) of the total rapamycin in the composition is in nanoparticles; (6) about 90% or more (or further provided herein) of the total albumin in the composition is in nanoparticles. (7) The composition contains 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 contains 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 contains an albumin stabilizer (caprylic acid derivative, e.g., sodium caprylate and / or tryptophan derivative, e.g., N-acetyltryptophanate); (10) After filtering the composition using a 0.2 micron filter, at least about 80% or more of the rapamycin in the composition (or as further provided herein) 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 at the same time at which it is not bound to albumin in the non-nanoparticle 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 distinct features (in addition to or instead of any one of the above distinct features): (1) the concentration of albumin in the composition is about 30 mg / mL to about 100 mg / mL (or further provided herein); (2) the concentration of rapamycin in the composition is about 1 mg / mL to about 15 mg / mL (or about 1 mg / mL to about 7 mg / mL, etc., further provided herein); (3) the gravimetric osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg (or further provided herein); (4) the viscosity of the composition is about 1.2 cP to about 1.5 cP (or further provided herein); and / or (5) the pH of the composition is about 6.0 to about 7.5 (or further provided herein).

[0140] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, has one or more of the following distinct characteristics: (1) about 80% to about 95% (or further provided herein) of the total albumin in the composition is in the form of monomeric albumin; (2) about 4% to about 15% (or 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 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 the total albumin in the composition to the total rapamycin is about 1:1 to about 10:1 (or further provided herein); (6) about 90% or more (or further provided herein) of the total rapamycin in the composition is in nanoparticles; (7) about 90% or less of the total albumin in the composition (1) The composition contains (or is further provided herein) rapamycin in the non-nanoparticle portion of the nanoparticles; (8) The composition contains tert-butanol at a concentration of less than about 10 μg / mL or less than about 10 ppm (or is further provided herein); (9) The composition contains chloroform at a concentration of less than about 5 μg / mL or less than about 5 ppm (or is further provided herein); (10) The composition contains an albumin stabilizer (caprylic acid derivative, e.g., sodium caprylate and / or tryptophan derivative, e.g., N-acetyltryptophanate); (11) After filtering the composition using a 0.2 micron filter, at least about 80% or more (or is 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-nanoparticle portion of the composition and is not bound to albumin in the non-nanoparticle portion of the composition.In some embodiments, the nanoparticle composition can be a nanoparticle suspension, and the nanoparticle composition can have one or more of the following distinct characteristics (in addition to, or instead of, any one of the said distinct characteristics): (1) the concentration of albumin in the composition is about 30 mg / mL to about 100 mg / mL (or as further provided herein); (2) the concentration of rapamycin in the composition is about 1 mg / mL to about 15 mg / mL (such as about 1 mg / mL to about 7 mg / mL, etc., as further provided herein); (3) the weight osmolality of the composition is about 300 mOsm / kg to about 350 mOsm / kg (or as otherwise provided herein); (4) the viscosity of the composition is about 1.2 cP to about 1.5 cP (or as otherwise provided herein); and / or (5) the pH of the composition is about 6.0 to about 7.5 (or as otherwise provided herein). <##

[0141] 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 distinct 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 a Z-average particle size of about 200 nm or less (such as 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 (such as about 0.03 to about 0.2, etc., as otherwise provided herein); (6) the range of the particle size distribution ((D v95 -D v5 ) / D v50(1) The nanoparticles are approximately 0.8 to approximately 1.2 (or otherwise provided herein); (7) The nanoparticles are approximately 25% to approximately 45% by weight (or otherwise provided herein) of albumin; (8) The nanoparticles are approximately 55% to approximately 75% by weight (or otherwise provided herein) of rapamycin; (9) The weight ratio of albumin in the nanoparticles to rapamycin is approximately 1:1 to approximately 1:4 (or otherwise provided herein); (10) The zeta potential of the nanoparticles in the composition is approximately -25mV to approximately -50mV (or otherwise provided herein); (11) nano (12) The particles have an amorphous form; (13) The rapamycin in the nanoparticles has an amorphous form; (14) The vinyl chain of rapamycin in the nanoparticles interacts with albumin in the nanoparticles; (15) At least a portion of the nanoparticles in the composition (e.g., at least 20%, or otherwise provided herein) are non-spherical; and / or (16) The nanoparticles contain less than about 2.5% by weight of seco-rapamycin (or about 0.2% to about 2.5% by weight, or otherwise provided herein) compared to the sum of seco-rapamycin and rapamycin. In some embodiments, the nanoparticle composition may 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 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 distinct characteristics: (1) about 25% to about 50% (or otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin monomers; (2) about 5% to about 16% (or otherwise provided herein) of the albumin in the nanoparticles is in the form of albumin dimers; (3) about 1% to about 4.5% (or otherwise provided herein) of the albumin in the nanoparticles is albumin oligomers. (4) The nanoparticles are in the form of albumin polymer (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, etc., as provided elsewhere herein) (6) The nanoparticles have a polydispersity index of less than about 0.2 (or between about 0.03 and about 0.2, etc., as provided elsewhere herein) (7) The particle size distribution range ((D v95 ~D v5 ) / D v50(1) The nanoparticles are approximately 0.8 to approximately 1.2 (or otherwise provided herein); (8) the nanoparticles are approximately 25% to approximately 45% by weight (or otherwise provided herein) of albumin; (9) the nanoparticles are approximately 55% to approximately 75% by weight (or otherwise provided herein) of rapamycin; (10) the weight ratio of albumin in the nanoparticles to rapamycin is approximately 1:1 to approximately 1:4 (or otherwise provided herein); (11) the zeta potential of the nanoparticles in the composition is approximately -25mV to approximately -50mV (or otherwise provided herein); (12) nano (13) The particles have an amorphous form; (14) The rapamycin in the nanoparticles has an amorphous form; (15) The vinyl chain of rapamycin in the nanoparticles interacts with albumin in the nanoparticles; (16) At least a portion of the nanoparticles in the composition (e.g., at least 20%, or otherwise provided herein) are non-spherical; and / or (16) The nanoparticles contain less than about 2.5% by weight of seco-rapamycin (or between about 0.2% by weight and about 2.5% by weight, or otherwise provided herein) compared to the sum of seco-rapamycin and rapamycin. In some embodiments, the nanoparticle composition may be a nanoparticle suspension, and in some embodiments, the concentration of albumin in the nanoparticle suspension present in the nanoparticles is about 1.8 mg / mL to about 3 mg / mL (or 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 distinct characteristics: (1) about 80% to about 95% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin monomers; (2) about 5% to about 14% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin dimers; and / or (3) about 1% to about 5% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin polymers (or albumin trimers). In some embodiments, the nanoparticle composition may be a nanoparticle suspension, the non-nanoparticle portion of the nanoparticle suspension may have one or more of the following distinct characteristics (in addition to or instead of any one of the aforementioned distinct characteristics): (1) the concentration of albumin in the non-nanoparticle portion of the composition is about 30 mg / mL to about 100 mg / mL (or otherwise provided herein); and / or (2) the concentration of rapamycin in the non-nanoparticle portion is about 20 μg / mL to about 55 μg / mL (or 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 distinct characteristics: (1) about 80% to about 95% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin monomers; (2) about 4% to about 14% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin dimers; and / or (3) about 0.5% to about 4% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of oligomers; and (4) about 0.5% to about 3% (or otherwise provided herein) of the albumin in the non-nanoparticle portion of the composition is in the form of albumin polymers (other than albumin oligomers). In some embodiments, the nanoparticle composition may be a nanoparticle suspension, the non-nanoparticle portion of the nanoparticle suspension may have one or more of the following distinct characteristics (in addition to or instead of any one of the aforementioned distinct 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 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 otherwise provided herein).

[0145] The compositions described herein (such as pharmaceutical compositions), or commercial batch compositions (such as pharmaceutical compositions), may be in liquid (e.g., as a nanoparticle suspension) or powder form. For example, in some embodiments, the composition is a liquid nanoparticle suspension (e.g., before lyophilization). In some embodiments, the composition is a reconstituted suspension (e.g., in an aqueous solution such as Seyline solution). In some embodiments, the composition is dried, e.g., lyophilized. The lyophilized composition is generally a white or slightly yellow lyophilized cake which may be crushed into a loose powder and / or reconstituted into an aqueous suspension. In some embodiments, the composition is sterile. In some embodiments, the composition is 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 containing rapamycin and albumin (such as human albumin), and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer 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 monomer 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 approximately 30 mg / mL to approximately 100 mg / mL. In some embodiments, the weight osmolality of the composition is approximately 300 mOsm / kg to approximately 350 mOsm / kg. In some embodiments, the viscosity of the composition is approximately 1.2 cP to approximately 1.5 cP. In some embodiments, the pH of the composition is approximately 6.0 to approximately 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.

[0147] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 dimer 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 weight 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 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.

[0148] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer 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 monomer 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 approximately 30 mg / mL to approximately 100 mg / mL. In some embodiments, the weight osmolality of the composition is approximately 300 mOsm / kg to approximately 350 mOsm / kg. In some embodiments, the viscosity of the composition is approximately 1.2 cP to approximately 1.5 cP. In some embodiments, the pH of the composition is approximately 6.0 to approximately 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.

[0149] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 dimer 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 weight 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 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.

[0150] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 70% to about 85% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer 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 weight 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 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.

[0151] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 dimer 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 gravimetric 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 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.

[0152] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 (such as 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 trimer 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 dimer 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 weight 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 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.

[0153] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 (such as 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 dimer 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 gravimetric 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 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.

[0154] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 5% to about 15% of the albumin in the nanoparticles is in the form of polymer albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 dimer 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 monomer 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 gravimetric 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 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.

[0155] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 42% to about 62% of the albumin in the nanoparticles is in the form of polymer albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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, rapamycin in 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.

[0156] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 5% to about 15% of the albumin in the nanoparticles is in the form of polymer albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer 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 monomer 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 weight 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 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.

[0157] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 42% to about 60% of the albumin in the nanoparticles is in the form of polymer albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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, rapamycin in nanoparticles is amorphous. 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.

[0158] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 9% to about 20% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer 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 monomer 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 gravimetric 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 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.

[0159] In some embodiments, the nanoparticle composition, or a commercial batch of the nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 5% to about 16% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 oligomer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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, rapamycin in nanoparticles is in 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.

[0160] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 9% to about 20% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer 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 monomer 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 weight 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 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.

[0161] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 5% to about 16% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer 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 dimer 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 gravimetric 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 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.

[0162] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where 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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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, rapamycin in nanoparticles is amorphous. 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.

[0163] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where 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 containing albumin (such as 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 or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 gravimetric 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 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.

[0164] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the gravimetric 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, rapamycin in the nanoparticles is amorphous. 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.

[0165] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing 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 (such as 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 dimer 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 a weight 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, rapamycin in the nanoparticles is in 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.

[0166] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a Z-mean particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), containing rapamycin and albumin (e.g., human albumin), where 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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing 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 trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the gravimetric 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, rapamycin in the nanoparticles is amorphous. 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.

[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), containing rapamycin and albumin (e.g., human albumin), where about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin, about 5% to about 16% is in the form of dimeric albumin, about 1% to about 4.5% is in the form of oligomeric albumin, and about 42% to about 60% is in the form of polymeric albumin (other than oligomeric albumin); and (b) a non-nanoparticle portion containing 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 dimer 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 a weight 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, rapamycin in the nanoparticles is in 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.

[0168] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles having a Z-mean particle size of about 200 nm or less (e.g., about 50 nm to about 200 nm), comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 concentration of total albumin in the nanoparticle composition is about 30 mg / mL to about 100 mg / mL. In some embodiments, the gravimetric 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, rapamycin in the nanoparticles is amorphous. 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.

[0169] 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), including a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 containing albumin (such as 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 dimer 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 weight 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 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.

[0170] 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), containing about 55% to about 65% by weight rapamycin and about 25% to about 45% by weight albumin (e.g., human albumin), with about 70% to about 85% of the albumin in the nanoparticles being in the form of monomeric albumin, about 9% to about 20% of the albumin in the nanoparticles being in the form of dimeric albumin, and about 5% to about 15% of the albumin in the nanoparticles being in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion containing 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 gravimetric 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 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.

[0171] 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), containing about 55% to about 65% by weight of rapamycin and about 25% to about 45% by weight of albumin (e.g., human albumin), where 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 containing 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 polymer 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 dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 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.

[0172] 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), including a coating containing albumin (e.g., human albumin) and a core containing rapamycin, where 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), where albumin constitutes about 25% to about 45% by weight of the nanoparticles and rapamycin constitutes about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion containing 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 gravimetric 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 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.

[0173] 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 a coating containing albumin (such as human albumin) and a core containing 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), with albumin constituting about 25% to about 45% by weight of the nanoparticles and rapamycin constituting about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer 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 dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 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.

[0174] 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), containing about 55% to about 75% by weight of rapamycin and about 25% to about 45% by weight of albumin (e.g., human albumin), where 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 containing 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 or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymer albumin (or trimer 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 dimer 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 monomer 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 a weight 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, rapamycin in the nanoparticles is in 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.

[0175] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 nanoparticle having a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.), containing about 55% to about 75% by weight of rapamycin and about 25% to about 45% by weight of albumin (such as human albumin); (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.). 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 polymerized 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 or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 weight 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 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.

[0176] 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), including a coating containing albumin (e.g., human albumin) and a core containing 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), with albumin constituting about 25% to about 45% by weight of the nanoparticles and rapamycin constituting about 55% to about 75% by weight of the nanoparticles; and (b) a non-nanoparticle portion containing 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 polymer albumin (or trimer 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 dimer 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 monomer 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 weight 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 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.

[0177] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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), with albumin making up about 25% by weight of the nanoparticles. (b) a nanoparticle having a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.), comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, with rapamycin making up 45% by weight, and rapamycin making up about 55% to about 75% by weight of the nanoparticles; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.). 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 polymer 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 or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 a weight 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 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.

[0178] In some embodiments, the nanoparticle composition, or commercial batch of the nanoparticle composition, (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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin), with about 55% to about 75% (by weight) of rapamycin and about 25% ( (b) a nanoparticle comprising (b) a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.) and a zeta potential of about -25 mV to about -50 mV, containing (b)% to about 45 (by weight)% of albumin (such as human albumin); and (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.). 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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 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.

[0179] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, is (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), with about 55% to about 7% by weight. (b) a nanoparticle comprising: (a) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is approximately 1 mg / mL to approximately 100 mg / mL (such as approximately 1 mg / mL to approximately 15 mg / mL). In some embodiments, approximately 0.5% to approximately 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymerized albumin (other than oligomeric albumin). In some embodiments, approximately 0.3% to approximately 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 or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 a weight 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 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.

[0180] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin), with albumin constituting about 25% to about 45% by weight of the nanoparticles, and rapamycin constituting about 55% to about 7% by weight of the nanoparticles. (b) a nanoparticle comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, with a Z-average particle size of about 200 nm or less (such as about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is about 1 mg / mL to about 100 mg / mL (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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 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.

[0181] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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), and albumin constitutes about 25% to about 45% by weight of the nanoparticles, (b) a nanoparticle comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, with a Z-average particle size of approximately 200 nm or less (such as approximately 50 nm to approximately 200 nm) and a zeta potential of approximately -25 mV to approximately -50 mV; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition is approximately 1 mg / mL to approximately 100 mg / mL (such as approximately 1 mg / mL to approximately 15 mg / mL). In some embodiments, approximately 0.5% to approximately 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymerized albumin (other than oligomeric albumin). In some embodiments, approximately 1% to approximately 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 a weight 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 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.

[0182] In some embodiments, the nanoparticle composition, or commercial batch of the nanoparticle composition, (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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin), with about 55% to about 75% by weight of rapamycin and about 25% to about 45% by weight of albumin. (b) a nanoparticle comprising (a) a nanoparticle having a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.) and a zeta potential of about -25 mV to about -50 mV, containing albumin (such as human albumin); (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.); and about 3% or less of the rapamycin in the nanoparticle composition being 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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 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.

[0183] In some embodiments, the nanoparticle composition, or commercial batch of the nanoparticle composition, (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), with about 55% to about 75% by weight of rapamycin and (b) a nanoparticle comprising: (a) a nanoparticle having a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.) and a zeta potential of about -25 mV to about -50 mV, containing 25 (by weight) to about 45 (by weight) of albumin (such as human albumin); (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.); and about 3% or less of the rapamycin in the nanoparticle composition being 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 polymerized 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 or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 a weight 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 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.

[0184] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer 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 albumin (hybrid albumin) (b) A nanoparticle comprising a coating containing (e.g., toalbumin) and a core containing rapamycin, 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; (b) a non-nanoparticle portion containing 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); and about 3% or less of the rapamycin in the nanoparticle composition being 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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 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.

[0185] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 constitutes about 25% to about 45% by weight of the nanoparticles, and rapamycin constitutes about 55% by weight of the nanoparticles. (b) a nanoparticle comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, with a Z-average particle size of approximately 200 nm or less (such as approximately 50 nm to approximately 200 nm) and a zeta potential of approximately -25 mV to approximately -50 mV; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition being approximately 1 mg / mL to approximately 100 mg / mL (such as approximately 1 mg / mL to approximately 15 mg / mL); and approximately 3% or less of the rapamycin in the nanoparticle composition being free rapamycin. In some embodiments, approximately 0.5% to approximately 7% of the albumin or total albumin in the non-nanoparticle portion of the nanoparticle composition is in the form of polymerized albumin (other than oligomeric albumin). In some embodiments, approximately 1% to approximately 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 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 weight 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 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.

[0186] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin), with about 55% to about 75% by weight of rapamycin and about 25% to about 45% by weight of albumin (such as human albumin). (b) a nanoparticle comprising: (a) 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; (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); and the total amount of seco-rapamycin and rapamycin in the nanoparticles being less than 3% by weight (e.g., about 0.2% to about 3% by weight). 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 gravimetric 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 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.

[0187] In some embodiments, the nanoparticle composition, or commercial batch of the nanoparticle composition, (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), with about 55% to about 75% by weight of rapamycin and about 25% to about 45% by weight (b) A nanoparticle comprising (a) a Z-average particle size of about 200 nm or less (about 50 nm to about 200 nm, etc.) and a zeta potential of about -25 mV to about -50 mV, containing )% albumin (such as human albumin); (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (about 1 mg / mL to about 15 mg / mL, etc.); and the total amount of seco-rapamycin and rapamycin in the nanoparticles being less than 3% by weight (about 0.2% to about 3% by weight, etc.). 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 polymer 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of dimer albumin. In some embodiments, about 80% to about 95% of the albumin in the non-nanoparticle portion of the nanoparticle composition or the total albumin is in the form of monomer 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 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 weight 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 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.

[0188] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) albumin (such as 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 dimer albumin, and about 5% to about 15% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin), the albumin constitutes about 25% to about 45% by weight of the nanoparticles, and rapamycin constitutes about 55% to about 75% by weight of the nanoparticles. (b) A nanoparticle comprising a core containing ting and rapamycin, 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; (b) a non-nanoparticle portion containing 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); and the total amount of seco-rapamycin and rapamycin in the nanoparticles being less than 3% by weight (e.g., about 0.2% to about 3% by weight). 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 80% to about 95% 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 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 weight 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 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.

[0189] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, (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 constitutes about 25% to about 45% by weight of the nanoparticles, and rapamycin constitutes about 55% to about 75% by weight of the nanoparticles, (b) A nanoparticle comprising a coating containing lubumin (such as human albumin) and a core containing rapamycin, having a Z-average particle size of about 200 nm or less (such as about 50 nm to about 200 nm) and a zeta potential of about -25 mV to about -50 mV; (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin; the concentration of rapamycin in the nanoparticle composition being about 1 mg / mL to about 100 mg / mL (such as about 1 mg / mL to about 15 mg / mL); and the total amount of seco-rapamycin and rapamycin in the nanoparticles being less than 3% by weight (such as 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 polymer 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 polymer 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 dimer 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 monomer 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 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 weight 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 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.

[0190] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 74% to about 80% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0191] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 25% to about 50% of the albumin in the nanoparticles is in the form of monomeric albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 dimer albumin. In some embodiments, about 4% to about 15% of the total albumin in the nanoparticle composition is in the form of dimer albumin. In some embodiments, about 80% to about 95% 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 nanoparticle composition 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 weight 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, rapamycin in the nanoparticles is amorphous. 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.

[0192] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0193] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 (such as 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 dimeralbumin. In some embodiments, about 4% to about 15% of the total albumin in the nanoparticle composition is in the form of dimeralbumin. In some embodiments, about 80% to about 95% 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 nanoparticle composition 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 weight 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, rapamycin in the nanoparticles is amorphous. 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.

[0194] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 7% to about 11% of the albumin in the nanoparticles is in the form of polymer albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0195] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 7% to about 11% of the albumin in the nanoparticles is in the form of polymer albumin (or trimer albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0196] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where about 12% to about 17% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0197] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where about 12% to about 17% of the albumin in the nanoparticles is in the form of dimer albumin; and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0198] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles containing rapamycin and albumin (such as human albumin), where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 nanoparticle composition 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 weight 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, rapamycin in the nanoparticles is amorphous. 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.

[0199] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises: (a) nanoparticles comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as human albumin) and rapamycin. In some embodiments, about 1.5% to about 3% of the albumin in the non-nanoparticle portion of the nanoparticle composition or of the total albumin is in the form of polymeric albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 nanoparticle composition 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 weight 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, rapamycin in the nanoparticles is in 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 (such as human albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0201] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a Z-mean particle size of about 85 nm to about 95 nm, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0202] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a Z-mean particle size of about 85 nm to about 95 nm, containing rapamycin and albumin (such as human albumin), where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0203] 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, containing rapamycin and albumin (such as human albumin), where 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 containing albumin (such as 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 in the non-nanoparticle portion of the nanoparticle composition or the total albumin 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 dimer albumin. In some embodiments, about 80% to about 95% 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 composition has a weight 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, rapamycin in the nanoparticles is in 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.

[0204] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a Z-mean particle size of about 85 nm to about 95 nm, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0205] 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 (such as human albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[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, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0207] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a zeta potential of about -33mV to about -39mV, containing rapamycin and albumin (such as human albumin), where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0208] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a zeta potential of about -33mV to about -39mV, in which 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 (other than 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 dimer 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 a weight 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, rapamycin in the nanoparticles is in 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.

[0209] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a zeta potential of about -33mV to about -39mV, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0210] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, comprises (a) nanoparticles having a Z-mean 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 (such as human albumin); and (b) a non-nanoparticle portion comprising albumin (such as 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 polymer albumin (or trimer 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 dimer 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 dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[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, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer 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 dimer 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 monomer 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 concentration of total albumin in the nanoparticle composition is about 35 mg / mL to about 45 mg / mL. In some embodiments, the weight 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 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.

[0212] 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, containing rapamycin and albumin (such as human albumin), where 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 dimer albumin, and about 7% to about 11% of the albumin in the nanoparticles is in the form of polymeric albumin (or trimer albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 weight 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 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.

[0213] 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, containing rapamycin and albumin (such as human albumin), where 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 containing albumin (such as 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 dimer 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 a weight 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 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.

[0214] 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, comprising a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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 containing albumin (such as 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 weight 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 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.

[0215] 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, containing about 62% to about 68% by weight rapamycin and about 32% to about 38% by weight albumin (such as human albumin), with about 74% to about 80% of the albumin in the nanoparticles being in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles being in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles being in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 weight 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 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.

[0216] 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, with about 62% to about 68% by weight of rapamycin and about 32% to about 38% by weight of albumin (such as human albumin), where 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 (such as 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 polymer 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 dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 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.

[0217] 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 a coating containing albumin (such as human albumin) and a core containing rapamycin, where 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), with albumin constituting about 32% to about 38% by weight of the nanoparticles and rapamycin constituting about 62% to about 68% by weight of the nanoparticles; and (b) a non-nanoparticle portion containing albumin (such as 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 weight 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, 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 within 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.

[0218] 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, containing about 62% to about 68% by weight of rapamycin and about 32% to about 38% by weight of albumin (such as human albumin), with about 74% to about 80% of the albumin in the nanoparticles being in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles being in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles being in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 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.

[0219] 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 a coating containing albumin (such as human albumin) and a core containing 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), with albumin constituting about 32% to about 38% by weight of the nanoparticles and rapamycin constituting about 62% to about 68% by weight of the nanoparticles; and (b) a non-nanoparticle portion containing albumin (such as 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 from 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 within 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.

[0220] 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, containing about 62% to about 68% by weight of rapamycin and about 32% to about 38% by weight of albumin (such as human albumin), with about 74% to about 80% of the albumin in the nanoparticles being in the form of monomeric albumin, about 12% to about 17% of the albumin in the nanoparticles being in the form of dimeric albumin, and about 7% to about 11% of the albumin in the nanoparticles being in the form of polymeric albumin (or trimeric albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 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 polymer albumin (or trimer 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 dimer albumin. In some embodiments, about 7% to about 11% of the total albumin in the nanoparticle composition is in the form of dimer 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 monomer 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 nanoparticles. In some embodiments, the concentration of albumin in the nanoparticle composition within 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 weight 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 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.

[0221] In some embodiments, a nanoparticle composition, or a commercial batch of a nanoparticle composition, is (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), with approximately 62% (weight) (b) a nanoparticle comprising (a) a nanoparticle with 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, containing (b)% to about 68 (by weight)% of rapamycin and about 32 (by weight)% to about 38 (by weight)% of albumin (such as human albumin); and (b) a non-nanoparticle portion containing albumin (such as 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 polymerized albumin (ot...

Claims

1. A nanoparticle composition comprising (a) nanoparticles containing rapamycin and albumin, and (b) a non-nanoparticle portion containing albumin and rapamycin, A nanoparticle composition in which, when the proportion of albumin in nanoparticles that is in the form of polymer albumin other than oligomeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, it is found that 42% to 60% of the albumin in the nanoparticles is in the form of polymer albumin other than oligomeric albumin.

2. The nanoparticle composition according to claim 1, wherein the nanoparticle composition contains seco-rapamycin and the zeta potential of the nanoparticles is -25 mV to -50 mV.

3. The nanoparticle composition according to claim 1 or 2, wherein the nanoparticle composition is a liquid composition, the Z-average particle size of the nanoparticles is 200 nm or less, the weight ratio of albumin to rapamycin in the composition is 1:1 to 10:1, the concentration of rapamycin in the composition is 50 mg / ml to 100 mg / ml, and the composition is stable at 25°C for at least 24 hours.

4. The nanoparticle composition according to any one of claims 1 to 3, wherein the proportion of albumin in nanoparticles in the form of oligomeric albumin is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, and it is determined that 1% to 4.5% of the albumin in the nanoparticles is in the form of oligomeric albumin.

5. The nanoparticle composition according to claim 4, wherein the proportion of albumin in nanoparticles in the form of monomeric albumin or dimer albumin is measured by separating the nanoparticles from the non-nanoparticle portion, dissolving the nanoparticles, and subjecting the dissolved nanoparticles to size exclusion chromatography, and the proportion of albumin in nanoparticles is in the form of monomeric albumin or dimer albumin.

6. The nanoparticle composition according to any one of claims 1 to 5, wherein the proportion of albumin in the non-nanoparticle portion, which is in the form of monomeric albumin, dimer albumin, oligomeric albumin, and / or polymer albumin other than oligomeric albumin, is measured by separating nanoparticles from the non-nanoparticle portion and subjecting the non-nanoparticle portion to size exclusion chromatography, and the proportion of albumin in the non-nanoparticle portion is in the form of monomeric albumin, the proportion of albumin in the non-nanoparticle portion is in the form of dimer albumin, the proportion of albumin in the non-nanoparticle portion is in the form of oligomeric albumin, and / or the proportion of albumin in the non-nanoparticle portion is in the form of polymer albumin other than oligomeric albumin.

7. The nanoparticle composition according to any one of claims 1 to 6, wherein when the proportion of monomer albumin, dimer albumin, oligomer albumin, and / or polymer albumin (other than oligomer albumin) in the composition is measured by subjecting the composition to size exclusion chromatography, 80% to 95% of the total albumin in the composition is in the form of monomer albumin, 4% to 15% of the total albumin in the composition is in the form of dimer albumin, 0.3% to 3% of the total albumin in the composition is in the form of oligomer albumin, and 2% to 7% of the total albumin in the composition is in the form of polymer albumin (other than oligomer albumin).

8. The nanoparticle composition according to any one of claims 1 to 7, wherein the composition comprises seco-rapamycin, and the amount of seco-rapamycin is 0.2% to 3% by weight of the total amount of seco-rapamycin and rapamycin in the composition.

9. The nanoparticle composition according to any one of claims 1 to 8, wherein less than 1% of the rapamycin in the composition is free rapamycin.

10. The nanoparticle composition according to any one of claims 1 to 9, wherein the volume-weighted average particle size of the nanoparticles is 200 nm or less.

11. The nanoparticle composition according to any one of claims 1 to 10, wherein the Z-average particle size of the nanoparticles is 200 nm or less.

12. The nanoparticle composition according to any one of claims 1 to 11, wherein the polydispersity index of the nanoparticles is less than 0.

3.

13. The range of the particle size distribution of nanoparticles ((D ｖ 95-D ｖ 5) / D ｖ The nanoparticle composition according to any one of claims 1 to 12, wherein 50) is 0.8 to 1.

2.

14. The nanoparticle composition according to any one of claims 1 to 13, wherein the weight ratio of albumin to rapamycin in the composition is 1:1 to 10:

1.

15. The nanoparticle composition according to any one of claims 1 to 14, wherein the albumin concentration in the composition is 50 mg / mL to 100 mg / mL.

16. The nanoparticle composition according to any one of claims 1 to 15, wherein the weight osmolality of the composition is 280 mOsm / kg to 400 mOsm / kg.

17. The nanoparticle composition according to any one of claims 1 to 16, wherein the viscosity of the composition is 1.2 cP to 1.5 cP.

18. The nanoparticle composition according to any one of claims 1 to 17, wherein the composition comprises tert-butanol, and the amount of tert-butanol in the composition is less than 10 μg / mL.

19. The nanoparticle composition according to any one of claims 1 to 18, wherein the zeta potential of the nanoparticles is -25 mV to -50 mV.

20. The nanoparticle composition according to any one of claims 1 to 19, wherein the composition has an amorphous form determined by measuring the degree of crystallinity of the freeze-dried form of the composition by X-ray diffraction, 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.

21. The nanoparticle composition according to any one of claims 1 to 20, wherein the albumin is human albumin.

22. More than 90% by weight of rapamycin in the composition is present in the nanoparticles. The nanoparticle composition according to any one of claims 1 to 21.

23. The nanoparticle composition according to any one of claims 1 to 22, wherein the nanoparticle composition comprises a caprylic acid derivative and / or a tryptophan derivative.

24. A dispersed organic phase comprising nanodroplets containing rapamycin dissolved in an organic solvent containing chloroform and tert-butanol, for use in forming the nanoparticle composition according to any one of claims 1 to 23, and Continuous aqueous phase containing albumin An emulsion containing, which may contain at least 20 grams of rapamycin.

25. The emulsion according to claim 24, wherein the organic solvent may contain 10% to 50% by volume of tert-butanol and 50% to 90% by volume of chloroform.

26. The emulsion according to claim 24 or 25, wherein the rapamycin concentration in the organic phase is 20 mg / mL to 500 mg / mL.

27. The emulsion according to any one of claims 24 to 26, wherein the nanodroplets have a Z-average particle size of 200 nm or less.

28. The emulsion according to any one of claims 24 to 27, wherein the Z-average particle size of the nanodroplets does not increase by more than 30% after the emulsion is stored at 4°C for 24 hours.

29. A method for preparing the nanoparticle composition according to any one of claims 1 to 23, comprising removing an organic solvent from the emulsion according to any one of claims 24 to 28.

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