Compositions for cancer therapeutics

Abstract

This invention describes therapeutic compositions, uses and methods using deciparticles for cancer drug delivery. Deciparticle compositions of this invention can be composed of one or more taxane drug compounds complexed with amphiphilic molecules. The amphiphilic molecules may comprise a polyethylene glycol hydrophilic oligomer and a fatty acid alkanoyl hydrophobic core.

Description

COMPOSITIONS FOR CANCER THERAPEUTICSTECHNICAL FIELD

[0001] This invention describes therapeutic compositions, uses and methods with deciparticles for cancer drugs. Deciparticles of this invention are complexes of active agents and amphiphiles which advantageously enhance delivery by circulatory routes. The compositions and method of this invention can be applied for use in treating cancer.BACKGROUND

[0002] Cancer drugs have been delivered by circulatory routes with actives loaded in protective particles such as liposomes, exosomes, and other small particles. Particles for these purposes can range from 50-250 nanometers in size.

[0003] Drawbacks of conventional therapies with such particles include early removal of the particles from circulation by innate processes which cut off the delivery route.

[0004] Further drawbacks of conventional therapies include slow or poor extravasation so that active agents do not reach target cells.

[0005] A drawback of conventional small particle drug formulations is the poor ability of the particles to exit blood vessels and enter into tissue to deliver drug.

[0006] What is needed are therapeutic compositions, uses and methods which can enhance drug potency and allow active agents to reach cells and be taken up.

[0007] There is an urgent need for new compositions, uses and methods for delivery of potent actives to cancer cells.BRIEF SUMMARY

[0008] This invention provides therapeutic deciparticle compositions, as well as their uses and methods for treating cancer. The deciparticle compositions can be composed of a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core. Therapeutic deciparticle compositions can be for use in treating or ameliorating the symptoms of cancer in a subject. Further, the therapeutic deciparticle compositions may be used in methods for treating or ameliorating the symptoms of cancer in a subject in need.

[0009] Embodiments of this invention include the following:

[0010] A deciparticle composition for treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid alkanoyl hydrophobic core.

[0011] A deciparticle composition for use in treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core.

[0012] A method for treating or ameliorating the symptoms of a disease in a subject in need, the method comprising: preparing a deciparticle composition comprising a complex of one or more drugs; an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core; and administering a therapeutically sufficient amount of the deciparticle composition to the subject.

[0013] The composition above, wherein the deciparticles have an average size of from 4 nm to about 35 nm, or from 4 nm to 20 nm, or from 4 nm to 18 nm.

[0014] The composition above, wherein the deciparticles have a dispersity of size of up to about 0.1, or up to about 0.2, or up to about 0.3, or up to about 0.4, or up to about 0.5.

[0015] The composition above, wherein the deciparticles are stable for at least one day stored at 5 °C.

[0016] The composition above, wherein the one or more drugs are poorly water- soluble cancer drugs or antineoplastic drugs.

[0017] The composition above, wherein the one or more drugs are taxane compounds.

[0018] The composition above, wherein the one or more drugs are paclitaxel, docetaxel, cabazitaxel, a salt or ester form of any of the foregoing, or a combination thereof.

[0019] The composition above, wherein the one or more drugs are mTOR kinase inhibitors.

[0020] The composition above, wherein the one or more drugs are selected from everolimus, rapamycin, ridaforolimus, temsirolimus, umirolimus, zotarolimus, dactolisib, voxtalisib, a salt or ester form of any of the foregoing, and a combination thereof.

[0021] The composition above, wherein the disease is cancer.

[0022] The composition above, wherein the disease is a pancreatic cancer, a melanoma, a skin cancer, a lung cancer, a breast cancer, a prostate cancer, a colorectal cancer, a kidney cancer, a stomach cancer, an ovarian cancer, a cervical cancer, a liver cancer, or a multiple myeloma.

[0023] The composition above, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having weight molecular weight Mw from 350 to 2,500, or 500 to 1,000.

[0024] The composition above, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having a number molecular weight MN from N=7 to N=56.

[0025] The composition above, wherein the hydrophobic core is a fatty acid analogue having a branched or unbranched C(3-22) alkyl tail, C(6-22) alkyl tail, or a branched or unbranched C(6-20) alkenyl tail comprising 1-3 carbon-carbon double bonds, and wherein the fatty acid tail is attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0026] The composition above, wherein the hydrophobic core has a log P from 5-7 and weight molecular weight less than 500.

[0027] The composition above, wherein the amphiphilic compound is selected from mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, mPEG-O- C22, mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG-O(CO)-C15, mPEG-O(CO)-C17, mPEG-O(CO)-C19, mPEG-O(CO)-C21, mPEG-NH(CO)-Cl 1, mPEG-NH(CO)-C13, mPEG-NH(CO)-Cl 5, mPEG-NH(CO)-C17, mPEG-NH(CO)-C19, mPEG-NH(CO)-C21, wherein mPEG has MN with N=12-22, or the amphiphilic molecules have one of thefollowing structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted alkyl or alkenyl, any of which can be terminated with -CH3, -OH, -COOH, C=O; where PEG can be linked to R1by an O, NH(CO), O(CO); and where PEG can be mPEG with molecular weight from about 340 to about 2,500.

[0028] The composition above, wherein the amphiphilic compound comprises 60 to 99.9 weight percent of the deciparticle composition.

[0029] The composition above, wherein the one or more drugs in total comprise 0.1 to 40 weight percent of the deciparticle composition.

[0030] The composition above, wherein the deciparticle composition is lyophilized to a solid lyophile form.

[0031] The composition above, wherein the deciparticle composition is reconstituted from a lyophilized form.

[0032] The composition above, wherein the deciparticle composition is used or administered in combination with a standard of care, cancer chemotherapy, and / or radiation therapy.

[0033] The composition above, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from an antimetabolite drug, an alkylating drug, and a targeted cancer drug.

[0034] The composition above, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from gemcitabine, temozolamide, bevacizumab, 5 -fluorouracil (antimetabolite drugs), cyclophosphamide, busulfan (alkylating drugs), a targeted monoclonal antibody cancer drug, an immune checkpoint inhibitor, and a tyrosine kinase receptor inhibitor.

[0035] The composition above, wherein the maximum solution concentration for administration of the deciparticle composition is from 5-50 mg / mL.

[0036] The composition above, wherein the maximum tolerated dose of the deciparticle composition is 500 mg / kg.

[0037] A composition, comprising: a pharmaceutically acceptable suspension of the deciparticle compositionabove in a solvent; and one or more cryoprotective compounds.

[0038] The composition above, wherein the one or more cryoprotective compounds is a dextrin compound, or a saccharide sugar compound, or a combination thereof.

[0039] The composition above, wherein the total amount of the cryoprotective compounds is from 1% to 40% (w / v) of the composition, or from 1% to 25% (w / v) of the composition.

[0040] A compound, comprising an amphiphilic molecule having one of the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted (C6- 22)alkyl, (C6-22)alkoxy or (C6-22)alkenyl, where R2is terminated with -H, -CH3, -OH, -COOH, C=O; wherein PEG is linked to R1by an O, NH(CO), O(CO); wherein PEG has molecular weight from about 300 to about 2,500.

[0041] The compound above, wherein PEG is mPEG with molecular weight from about 340 to about 2,500.

[0042] The compound above, wherein the amphiphilic molecule is mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, or mPEG-O-C22, wherein mPEG has molecular weight from about 340 to about 2,500.

[0043] The compound above, comprising mPEG-O-C18, wherein mPEG has molecular weight 550.

[0044] The compound above, comprising mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG-O(CO)-C15, mPEG-O(CO)-C17, mPEG-O(CO)-C19, or mPEG-O(CO)-C21, wherein mPEG has molecular weight from about 340 to about 2,500.

[0045] The compound above, comprising mPEG-O(CO)-C17, wherein mPEG has molecular weight 550.

[0046] The compound above, comprising mPEG-NH(CO)-Cl 1, mPEG-NH(CO)-C13, mPEG-NH(CO)-Cl 5, mPEG-NH(CO)-C17, mPEG-NH(CO)-C19, or mPEG-NH(CO)- C21, wherein mPEG has molecular weight from about 340 to about 2,500.

[0047] The compound above, comprising mPEG-NH(CO)-C17, wherein mPEG has molecular weight 550.

[0048] A method for making a deciparticle composition above, the method comprising: mixing the one or more drugs in an organic solvent; contacting the amphiphilic compound with the drugs in the organic solvent; mixing or vortexing the organic solvent; filtering the deciparticle composition in the organic solvent to remove particles or aggregates larger than 15 nm, or 30 nm, or 75 nm, or 100 nm; and removing residual organic solvent and / or free drug from the deciparticle composition. A deciparticle composition made by the method above.

[0049] This invention further contemplates deciparticle compositions for use in the preparation of a medicament for treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid alkanoyl hydrophobic core.BRIEF DESCRIPTION OF THE DRAWINGS

[0050] FIG. 1 shows measured deciparticle sizes in working examples of this invention can be influenced by the number of carbon atoms in the hydrophobic core portion of the conjugate.

[0051] FIG. 2 shows some molecular tail structures for hydrophobic core moieties of the conjugate.

[0052] FIG. 3 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O-C12 and everolimus.

[0053] FIG. 4 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-C17 and everolimus.

[0054] FIG. 5 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O(CO)-(CH2)2CO2H and everolimus.

[0055] FIG. 6 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O(CO)-(CH2)3CO2H and everolimus.

[0056] FIG. 7 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O-C12 and paclitaxel.

[0057] FIG. 8 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-C17 and paclitaxel.

[0058] FIG. 9 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-(CH2)2CO2H and paclitaxel.

[0059] FIG. 10 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O(CO)-(CH2)2CO2H and paclitaxel.

[0060] FIG. 11 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O(CO)-(CH2)3CO2H and paclitaxel.

[0061] FIG. 12 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-(CH2)3CO2H and paclitaxel.

[0062] FIG. 13 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-Cl 1 and paclitaxel.

[0063] FIG. 14 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-NH(CO)-C15 and paclitaxel.

[0064] FIG. 15 shows deciparticle size and distribution measured for deciparticle compositions of this invention made with mPEG(550)-O-C18 and paclitaxel.DETAILED DESCRIPTION OF THE DISCLOSURE

[0065] This invention provides therapeutic deciparticle compositions, uses and methods for cancer therapy.

[0066] Deciparticles of this invention can be about 1 / 10ththe size of conventional nanoparticles used for drug delivery.

[0067] A deciparticle can have an average size of from 1 nm to 50 nm, or from 2 nm to 50 nm, or from 4 nm to 50 nm, or from 5 nm to 40 nm, or from 5 nm to 30 nm, or from 5 nm to 25 nm.

[0068] In some embodiments, a deciparticle may have an average size of from 5 nm to 20 nm, or from 5 nm to 15 nm.

[0069] In certain embodiments, a deciparticle may have an average size of less than 30 nm, or less than 15 nm.

[0070] In additional embodiments, a deciparticle may have an average size of about 4 to about 15 nm, or about 4 to about 12 nm, or about 8-18 nm.

[0071] In further embodiments, a deciparticle may have an average size of from about 4 nm to about 35 nm, or from 4 nm to 20 nm, or from 4 nm to 18 nm.

[0072] Deciparticles may have a dispersity of size of up to about 0.1, or up to about 0.2, or up to about 0.3, or up to about 0.4, or up to about 0.5.

[0073] In some aspects, this invention provides deciparticle compositions which are stable and can be lyophilized and reconstituted in aqueous suspension.

[0074] As used herein, the term particle size can refer to the average of the largest diameters of a collection of small particles.

[0075] Because the deciparticle compositions can achieve surprisingly small size particles, sometimes 1 / 10ththe size of conventional nanoparticles, the deciparticle compositions can provide improved transport of drug through blood vessel walls.

[0076] As used herein, the term “deciparticle” can relate to a small particle composition as further defined herein, which may also be referred to as a “therapeutic particle” or “nanoparticle.” The terms “deciparticle,” “therapeutic particle,” and “nanoparticle” may be used interchangeably throughout this description to describe the substances disclosed.

[0077] As described herein, a deciparticle composition may comprise a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs with an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core.

[0078] As used herein, the term deciparticle can refer to small particles (nanoparticles) composed of discrete amphiphilic molecules of this disclosure complexed with one or more drugs. A drug can be any lipophilic drug molecule, for example a poorly water-soluble drug which can be contacted with the amphiphilic molecules.

[0079] Particle size characteristics can be determined as known in the art, for example using a ZETASIZER particle analyzer (Malvern).

[0080] Deciparticle (nanoparticle) compositions can be made with amphiphilic molecules which are each a conjugate of a hydrophilic oligomer with a hydrophobic core.

[0081] Examples of hydrophilic oligomers are polyethylene glycols.

[0082] In some embodiments, a hydrophilic oligomer of this disclosure can be a polyethylene glycol or mPEG having weight molecular weight from 350 to 2,500, or 350 to 1,000, or 500 to 1,000. As used herein, the term mPEG can refer to methoxy -terminated PEG or methyl- terminated PEG.

[0083] In further embodiments, a hydrophilic oligomer of this disclosure can be a polyethylene glycol or mPEG having a number molecular weight MN from N=7 to about N=56.

[0084] Examples of hydrophobic cores include fatty acid analogue tails.

[0085] In some embodiments, a hydrophobic core can be a fatty acid analogue having a branched or unbranched C(3-22) alkyl tail, C(6-22) alkyl tail, or a branched or unbranched C(6- 22) alkenyl tail comprising 1-3 carbon-carbon double bonds. The fatty acid tail may be attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0086] In further embodiments, a hydrophobic core can be a fatty acid analogue having a branched or unbranched C(6-22) alkyl tail, C(9-22) alkyl tail, or a branched or unbranched C(9- 22) alkenyl tail comprising 1-3 carbon-carbon double bonds. The fatty acid tail may be attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0087] In additional embodiments, a hydrophobic core can be a fatty acid analogue having a branched or unbranched C(9-22) alkyl tail, C(12-22) alkyl tail, or a branched or unbranched C(12-22) alkenyl tail comprising 1-3 carbon-carbon double bonds. The fatty acid tail may be attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0088] In certain embodiments, a hydrophobic core can be a fatty acid analogue having a branched or unbranched C(12-22) alkyl tail, C(14-22) alkyl tail, or a branched or unbranched C(14-22) alkenyl tail comprising 1-3 carbon-carbon double bonds. The fatty acid tail may be attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0089] Examples of tail structures for hydrophobic core include lipophilic tails derived from a naturally-occurring or synthetic lipid, phospholipid, glycolipid, triacylglycerol, glycerophospholipid, sphingolipid, ceramide, sphingomyelin, cerebroside, or ganglioside, wherein the tail may contain a steroid.

[0090] Examples of tail structures for a hydrophobic core include substituted or unsubstituted C(3-22)alkyl, C(6-18)cycloalkyl, C(6-18)cycloalkyl-C(3-22)alkyl, C(3-22)alkenyl, C(3- 22)alkynyl, C(3-22)alkoxy, and C(6-18)alkoxy-C(3-22)alkyl.

[0091] Examples of tail structures for a hydrophobic core include substituted or unsubstituted C(6-22)alkyl, C(9-18)cycloalkyl, C(9-18)cycloalkyl-C(6-22)alkyl, C(6-22)alkenyl, C(6- 22)alkynyl, C(6-22)alkoxy, and C(9-18)alkoxy-C(6-22)alkyl.

[0092] Examples of tail structures for a hydrophobic core include substituted or unsubstituted C(9-22)alkyl, C(12-18)cycloalkyl, C(12-18)cycloalkyl-C(9-22)alkyl, C(9-22)alkenyl, C(9- 22)alkynyl, C(9-22)alkoxy, and C(12-18)alkoxy-C(9-22)alkyl.

[0093] Examples of tail structures for a hydrophobic core include substituted or unsubstituted methoxy-ethoxy-, methoxy-propoxy-, methoxy-butoxy-, methoxy-pentyloxy-, and methoxy- hexoxy-.

[0094] Examples of tail structures for a hydrophobic core include tails from myristic acid (C14:0)alkenyl, palmitic acid (C16:0)alkenyl, stearic acid (C18:0)alkenyl, oleic acid (Cl 8:1, double bond at carbon 9)alkenyl, linoleic acid (C18:2, double bond at carbon 9 or 12)alkenyl, linonenic acid (C18:3, double bond at carbon 9, 12, or 15)alkenyl, arachidonic acid (C20:4, double bond at carbon 5, 8, 11, or 14)alkenyl, and eicosapentaenoic acid (C20:5, double bond at carbon 5, 8, 11, 14, or 17)alkenyl. Other examples of fatty acid-like tails are found at Donald Voet and Judith Voet, Biochemistry, 3rd Edition (2005), p. 383.

[0095] Some example of hydrophobic tails for the hydrophobic core are given in FIG. 2.

[0096] A shorthand notation may be used for certain amphiphilic molecules of this disclosure. For example, CH3(OCH2CH2)nO(CH2)nCH3 may be designated as mPEG(550)-O- C12, where n is 12. mPEG(550) refers to methoxy- or methyl-terminated polyethylene glycol with relative molecular weight 550.

[0097] Examples of structures for a hydrophobic core include substituted or unsubstituted succinyl moieties.

[0098] Amphiphilic molecules of this invention may be made by methods known in the art. In some embodiments, deciparticles (nanoparticles) can be made wherein the hydrophilic oligomer may have a dispersity of molecular weight. For example, as known in the art, a polyethyleneglycol (PEG) portion of a molecule may have a dispersity of molecular weights around an average value. As used herein, it is understood that for a hydrophilic oligomer having a dispersity of molecular weight, a discrete, single moiety of a particular averagemolecular weight can also be used. For example, a polyethyleneglycol-550 moiety may have a range of molecular weights around an average of 550. In certain embodiments, a polyethyleneglycol moiety can be a single polyethyleneglycol moiety having a single molecular weight close to 550.

[0099] Examples of amphiphilic molecules of this disclosure for making deciparticle compositions include mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-0- C20, mPEG-O-C22, mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG-O(CO)-C15, mPEG- O(CO)-C17, mPEG-O(CO)-C19, mPEG-O(CO)-C21, mPEG-NH(CO)-Cl 1, mPEG-NH(CO)- C13, mPEG-NH(CO)-C15, mPEG-NH(CO)-C17, mPEG-NH(CO)-C19, and mPEG-NH(CO)- C21. The mPEG potion can have a MN with N=7-56, and can have a molecular weight from 350 to 2,500, or 350 to 1,000, or 500 to 1,000.

[0100] Referring to FIG. 2, examples of amphiphilic molecules of this disclosure for making deciparticle compositions include mPEG-O-C14(l), mPEG-O-C16(l), mPEG-O-C18(l), mPEG- O-C18(2), and mPEG-O-C18(3).

[0101] Examples of amphiphilic molecules of this disclosure include the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted alkyl or alkenyl, any of which can be terminated with -CEE, -OH, -COOH, or -C=O; where PEG can be linked to R1by an O, NH(CO), O(CO); and where PEG can be mPEG with molecular weight from about 340 to about 2,500.

[0102] Examples of amphiphilic molecules of this disclosure include the following structures:

[0103] mPEG-NH(CO)-C17, where n=7 to 56, mPEG MW 340 to 2,500.

[0112] As used herein, the term "alkyl" can refer to a saturated, branched or unbranched, substituted or unsubstituted aliphatic group containing from 1 to 22 carbon atoms. This definition applies to the alkyl portion of other groups. As used herein, the term “C(l-5)alkyl,” for example, includes C(l)alkyl, C(2)alkyl, C(3)alkyl, C(4)alkyl, and C(5)alkyl. Likewise, the term “C(3-22)alkyl,” for example, includes C(l)alkyl, C(2)alkyl, C(3)alkyl, C(4)alkyl, C(5)alkyl, C(6)alkyl, C(7)alkyl, C(8)alkyl, C(9)alkyl, C(10)alkyl, C(l l)alkyl, C(12)alkyl, C(13)alkyl, C(14)alkyl, C(15)alkyl, C(16)alkyl, C(17)alkyl, C(18)alkyl, C(19)alkyl, C(20)alkyl, C(21)alkyl, and C(22)alkyl.

[0113] As used herein, the term "alkenyl" can refer to an unsaturated, branched or unbranched, substituted or unsubstituted alkyl or cycloalkyl having 2 to 22 carbon atoms and at least one carbon-carbon double bond.

[0114] As used herein, the term "alkynyl" can refer to an unsaturated, branched or unbranched, substituted or unsubstituted alkyl or cycloalkyl having 2 to 22 carbon atoms and at least one carbon-carbon triple bond.

[0115] As used herein, the term "substituted" can refer to an atom having one or more substitutions or substituents which can be the same or different and may include a hydrogen substituent. Thus, the terms alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkanoyl, alkanoyloxy, alkylamino, alkylaminoalkyl, aryl, heteroaryl, heterocycle, aroyl, and aralkyl as used herein refer to groups which include substituted variations. Substituted variations include linear, branched, and cyclic variations, and groups having a substituent or substituents replacing one or more hydrogens attached to any carbon atom of the group. Substituents that may be attached to a carbon atom of the group include alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkanoyl, alkanoyloxy, alkylamino, alkylaminoalkyl, aryl, heteroaryl, heterocycle, aroyl, aralkyl, acyl, hydroxyl, cyano, halo, haloalkyl, amino, aminoacyl, alkylaminoacyl, acyloxy, aryloxy, aryloxyalkyl, mercapto, nitro, carbamyl, carbamoyl, and heterocycle. For example, the term ethyl includes without limitation -CH2CH3, -CHFCH3, -CF2CH3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, — CF2CHF2, -CF2CF3, and other variations as described above. In general, substituents may be further substituted with any atom or group of atoms.

[0116] In general, a compound may contain one or more chiral centers. Compounds containing one or more chiral centers may include those described as an "isomer," a "stereoisomer," a "diastereomer," an "enantiomer," an "optical isomer," or as a "racemic mixture." Conventions for stereochemical nomenclature, for example the stereoisomer naming rules of Cahn, Ingold and Prelog, as well as methods for the determination of stereochemistry and the separation of stereoisomers are known in the art. See, for example, Michael B. Smith and Jerry March, March’s Advanced Organic Chemistry, 5th edition, 2001. The compounds and structures of this disclosure are meant to encompass all possible isomers, stereoisomers, diastereomers, enantiomers, and / or optical isomers that would be understood to exist for the specified compound or structure, including any mixture, racemic or otherwise, thereof.

[0117] Some compounds, peptides and / or protein compositions of this invention may have one or more chiral centers and / or geometric isomeric centers (E- and Z-isomers), and it is to be understood that the invention encompasses all such optical isomers, diastereoisomers, geometric isomers, and mixtures thereof.

[0118] This invention encompasses any and all tautomeric, solvated or unsolvated, hydrated or unhydrated forms, as well as any atom isotope forms of the compounds, peptides and / or protein compositions disclosed herein.

[0119] Deciparticle compositions of this invention may fall in a new regime of size and molecular mass and can be formed from discrete amphiphilic molecules of this disclosure which are not block copolymers.

[0120] In some embodiments, deciparticles (nanoparticles) can have an average size of from 1 nm to 50 nm, 5 nm to 50 nm, or from 5 nm to 30 nm, or from 5 nm to 25 nm, or from 5 nm to 15 nm, or less than 30 nm, or less than 15 nm, or about 1-15 nm, or about 10-15 nm.

[0121] In some embodiments, deciparticle compositions of this invention can be made from amphiphilic molecules, where the amphiphilic molecules comprise 60 to 99.9 weight percent of the deciparticle composition.

[0122] In further embodiments, deciparticle compositions of this invention can be made to include one or more drugs complexed with an amphiphilic molecule of this disclosure.

[0123] In certain embodiments, deciparticle compositions of this invention can be made to include one or more cancer drugs, where the drugs comprise in total 0.1 to 40 weight percent of the deciparticle composition.

[0124] A deciparticle composition of this invention can be made to include one or more cancer drugs, so that the deciparticle composition is a pharmaceutical composition.

[0125] A deciparticle composition of this invention can be lyophilized to a solid lyophile form. A solid lyophile form made from a deciparticle composition can be reconstituted to form an aqueous suspension.

[0126] A deciparticle composition of this invention can be administered in combination with a standard of care for a disease, or in combination with another drug used for treating the same disease.

[0127] In some embodiments, a deciparticle composition of this invention can be administered in combination with a cancer chemotherapy, and / or a cancer radiation therapy.

[0128] In certain embodiments, a deciparticle composition can be administered in combination with a cancer drug selected from an antimetabolite drug, an alkylating drug, and a targeted cancer drug.

[0129] A deciparticle composition may be administered in combination with a cancer drug selected from gemcitabine, temozolamide, bevacizumab, 5 -fluorouracil (antimetabolite drugs), cyclophosphamide, busulfan (alkylating drugs), a targeted monoclonal antibody cancer drug, an immune checkpoint inhibitor, and a tyrosine kinase receptor inhibitor.

[0130] In certain embodiments, a maximum solution concentration for administration of the drugs using the deciparticle composition may be about 5-50 mg / mL.

[0131] In further embodiments, a maximum tolerated dose of a deciparticle composition may be about 500 mg / kg.

[0132] To prepare a product of this invention, a pharmaceutically acceptable suspension of deciparticles in a solvent can be used. A pharmaceutically acceptable suspension of deciparticles can optionally be prepared by adding one or more cryoprotective compounds. The deciparticles can be composed of one or more drugs.

[0133] In some embodiments, cryoprotective compounds can be a dextrin compound, or a saccharide sugar compound, or a combination thereof.

[0134] Examples of pharmaceutically acceptable excipients and components are given in Remington, The Science and Practice of Pharmacy, 21st ed., 2005; Rowe et al., Handbook of Pharmaceutical Excipients, 6th ed., 2012; Ash, Handbook of Pharmaceutical Additives, 3rd ed., 2007; Gibson, Pharmaceutical Preformulation and Formulation, 2nd ed., 2009.

[0135] In some embodiments, the total amount of the dextrin and sugar compounds can be from 1% to 40% (w / v) of the composition.

[0136] In certain embodiments, the dextrin compound may be from 20 % to 90% (w / v) of the total amount of the dextrin and sugar compounds.

[0137] Examples of solvent include water, a HEPES buffer, a phosphate buffer, a citrate buffer, or a buffer containing tris(hydroxymethyl)aminomethane.

[0138] Examples of a dextrin compound include substituted and unsubstituted cyclodextrins. In some embodiments, the dextrin compound can be a sulfobutyl ether cyclodextrin or a methyl-P-cyclodextrin.

[0139] In certain embodiments, the dextrin compound may be combined with an adsorbate excipient compound.

[0140] In further embodiments, the saccharide sugar compound may be a monosaccharide or disaccharide sugar compound, or may be selected from sucrose, lactose, lactulose, maltose, trehalose, cellobiose, and mannobiose.

[0141] Embodiments of this invention further contemplate processes for making a solid lyophile of deciparticles. The deciparticles may be composed of one or more drugs. A process for making a solid lyophile may comprise lyophilizing a suspension of a deciparticle composition described herein. This invention further provides a solid lyophile made by such processes, which solid lyophile can be stable for at least one day stored at 5°C or lower.

[0142] This invention may further include a process for making a drug product by reconstituting a solid lyophile described herein.

[0143] In some embodiments, processes of this invention include making a drug product or deciparticle suspension by the steps of: preparing a deciparticle composition from amphiphilic molecules which are each a conjugate of a hydrophilic oligomer with a hydrophobic core, suspending the deciparticle in a solvent, lyophilizing the suspension of deciparticles to form a solid lyophile material, reconstituting the drug product as a suspension of the solid lyophile.

[0144] In some aspects, a drug product may have low immunogenicity and may be administered in the absence of any steroid medicament.

[0145] In further aspects, the drug product may have low particle aggregation after being reconstituted.

[0146] In additional embodiments, a complete process for making a drug product or deciparticle suspension can include the steps: preparing deciparticles, wherein the deciparticles are composed of one or more drugs; preparing a suspension of the deciparticles in a pharmaceutically acceptable solvent; adding a dextrin compound to the solution containing the deciparticles; adding a saccharide sugar compound to the solution containing the deciparticles; lyophilizing the suspension containing the deciparticles to form a solid lyophile; and reconstituting the solid lyophile in the same or different pharmaceutically acceptable solvent to form the drug product.

[0147] In certain embodiments, the total amount of the dextrin and saccharide sugar compounds can be from 1% to 40% (w / v) of the suspension containing the deciparticles, or from 1% to 25% (w / v) of the suspension containing the deciparticles.

[0148] In various embodiments of this disclosure, the dextrin compound can be from 20% to 90% (w / v) of the total amount of the dextrin and saccharide sugar compounds.

[0149] A drug product of this invention may be stable for at least one day stored at 5°C.

[0150] A deciparticle composition of this invention may be stable for at least one day stored at 5°C.

[0151] A drug product of this invention may comprise deciparticles (nanoparticles) having an average size from 1 nm to 50 nm, 5 nm to 50 nm, or from 5 nm to 30 nm, or from 5 nm to 25 nm, or from 5 nm to 15 nm, or less than 30 nm, or less than 15 nm, or about 1-15 nm, or about 10-15 nm.

[0152] A deciparticle composition, suspension, or drug product of this invention may contain one or more anti-cancer drugs. The anti-cancer drugs can be used for treatment of any of pancreatic cancer, a melanoma, a skin cancer, a lung cancer, a breast cancer, a prostate cancer, a colorectal cancer, a kidney cancer, a stomach cancer, an ovarian cancer, a cervical cancer, a liver cancer, or a multiple myeloma, among others.

[0153] The one or more drugs of a deciparticle composition may be paclitaxel, docetaxel, cabazitaxel, a salt or ester form of any of the foregoing, or any combination thereof.

[0154] Examples of solvents include water, a HEPES buffer, a phosphate buffer, a citrate buffer, a buffer containing tris(hydroxymethyl)aminomethane, sterile water, water for injection, sterile normal saline, bacteriostatic water for injection, and a nebulizer solution.

[0155] In some embodiments, a solvent may comprise an antioxidant excipient.

[0156] Examples of a dextrin compound include substituted and unsubstituted cyclodextrins, as well as sulfobutyl ether cyclodextrins and methyl-P-cyclodextrins.

[0157] A process of this invention may include dextrin compound combined with an adsorbate excipient compound.

[0158] Examples of a saccharide sugar compound include monosaccharides and disaccharide sugar compounds, as well as sucrose, lactose, lactulose, maltose, trehalose, cellobiose, and mannobiose.

[0159] In certain embodiments, a drug product may be reconstituted in a time period of less than 120 seconds, or 180 seconds, or longer.

[0160] Embodiments of this invention further contemplate deciparticle compositions, suspensions, and drug products made by a process which can comprise the steps: preparing deciparticles with the amphiphilic molecules; purifying a deciparticle solution or suspension to remove residual reagents; filtering deciparticles to remove particles or aggregates larger than 15 nm, or 30 nm, or 75 nm, or 100 nm.

[0161] In some embodiments, deciparticle compositions, suspensions, and drug products can be made by a process which can comprise the steps of: preparing deciparticles with the amphiphilic molecules; purifying a deciparticle solution or suspension to remove residual reagents; filtering the deciparticles to remove particles or aggregates larger than 15 nm, or 30 nm, or 75 nm, or 100 nm.

[0162] In further embodiments, a process for making deciparticle compositions of this invention may have the following steps: heating the bulk conjugate amphiphilic molecule at up to 60°C, or until it is liquid; adding one or more lipophilic drugs in solvent such as ethanol, while maintain heating; evaporating off the solvent from the mixture; resuspending the residue in water or solvent; adding bulking agent such as lactose; filtering to sterile; lyophilizing the sterile mixture.

[0163] In some aspects, the one or more drugs which comprise a deciparticle may be attached to a deciparticle, or adsorbed or absorbed by a deciparticle, or incorporated within the interior of a deciparticle.

[0164] Examples of drugs that can be incorporated into deciparticles of this invention include cytotoxic agents.

[0165] Examples of drugs that can be incorporated into deciparticles of this invention include cytostatic agents, cytotoxic agents, and DNA interactive agents. As used herein, the term incorporated into may include encapsulation.

[0166] Examples of drugs that can be incorporated into deciparticles of this invention include gemcitabine, cisplatin, doxorubicin, taxanes, taxotere, taxol, etoposide, irinotecan, camptostar,topotecan, paclitaxel, docetaxel epothilones, tamoxifen, thymidylate, 5-fluorouracil, methotrexate, temozolomide, cyclophosphamide, ara-C, adriamycin, and cytoxan.

[0167] Examples of drugs that can be incorporated into deciparticles (nanoparticles) of this invention include topoisomerase II inhibitors, topoisomerase I inhibitors, tubulin interacting agents, hormonal agents, synthase inhibitors, anti-metabolites, and alkylating agents.

[0168] Examples of drugs that can be incorporated into deciparticles of this invention include uracil mustard, chlormethine, ifosfamide, melphalan, chlorambucil, pipobroman, triethylenemelamine, triethylenethiophosphoramine, busulfan, carmustine, lomustine, streptozocin, dacarbazine, floxuridine, cytarabine, 6-mercaptopurine, 6-thioguanine, fludarabine phosphate, oxaliplatin, leucovirin, oxaliplatin, pentostatine, vinblastine, vincristine, vindesine, bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mithramycin, deoxy coformycin, mitomycin-C, L-asparaginase, teniposide, 17-alpha-ethinylestradiol, diethylstilbestrol, testosterone, prednisone, fluoxymesterone, dromostanolone propionate, testolactone, megestrolacetate, methylprednisolone, methyltestosterone, prednisolone, triamcinolone, chi orotriani sene, hydroxyprogesterone, aminoglutethimide, estramustine, medroxyprogesteroneacetate, leuprolide, flutamide, toremifene, goserelin, cisplatin, carboplatin, hydroxyurea, amsacrine, procarbazine, mitotane, mitoxantrone, levamisole, navelbene, anastrazole, letrazole, capecitabine, reloxafine, droloxafine, and hexamethylmelamine.

[0169] Examples of drugs that can be incorporated into deciparticles of this invention include a taxane compound and a platin compound.

[0170] Examples of drugs that can be incorporated into deciparticles of this invention include a paclitaxel, a docetaxel, a cisplatin, a carboplatin, an oxaliplatin, or any combination thereof.

[0171] Examples of drugs that can be incorporated into deciparticles of this invention include paclitaxel, carboplatin, rapamycin, everolimus, and palbociclib.

[0172] Examples of drugs that can be incorporated into deciparticles of this invention include a taxane compound and a platin compound include a combination of paclitaxel and cisplatin.

[0173] Examples of drugs that can be incorporated into deciparticles of this invention include paclitaxel, a docetaxel, a cisplatin, a carboplatin, an oxaliplatin.

[0174] Examples of drugs that can be incorporated into deciparticles of this invention include (1) antimetabolite drugs, (2) alkylating drugs, (3) targeted cancer drugs, (4) immune checkpoint inhibitors, and (5) tyrosine kinase receptor inhibitors.

[0175] Embodiments of this invention further contemplate uses and methods wherein a deciparticle composition is administered in combination with a cancer drug selected from gemcitabine, temozolamide, bevacizumab, 5 -fluorouracil (antimetabolite drugs), cyclophosphamide, busulfan (alkylating drugs), targeted monoclonal antibody cancer drugs, immune checkpoint inhibitors, and tyrosine kinase receptor inhibitors. The drugs can be used or administered concurrently, simultaneously, sequentially, or separately in time.

[0176] Examples of immune checkpoint inhibitor agents include inhibitors of CTLA-4, PD-1, and PD-L1.

[0177] Examples of an immunotherapeutic agent of this disclosure include interleukins, a natural or synthetic IL-2, a high dose IL-2, a recombinant IL-2, and aldesleukin.

[0178] In certain embodiments, a checkpoint inhibitor of this disclosure may be pembrolizumab, nivolumab, cemiplimab, spartalizumab, atezolizumab, avelumab, or durvalumab.

[0179] Embodiments of this invention include methods for treating or ameliorating the symptoms of cancer in a human or animal subject in need, by administering a therapeutically sufficient amount of a deciparticle composition, suspension, or drug product of this invention.

[0180] The deciparticle compositions, suspensions, and drug products of this invention can be used to treat a disease requiring the administration of a drug, which may be contained in the deciparticle compositions, suspensions, or drug products.

[0181] The deciparticles of this invention can be made by covalent attachment of a hydrophilic oligomer to a hydrophobic core to form a conjugate amphiphilic molecule, which is then contacted with one or more drug molecules.

[0182] The deciparticles of this invention can include one or more drugs which can be hydrophobic drugs incorporated within the interiors of the deciparticles.

[0183] A pharmaceutical composition may be in unit dosage form, or in unit doses containing one or more active components. A unit dosage form can be a kit or packaged format containing one or more unit doses, such as tablets, capsules, and powders in vials or ampoules.

[0184] In some embodiments, a composition can deliver the actives in a sustained release formulation or extended-release formulation.

[0185] The actives in a composition of this invention can be administered at an initial dosage of from about 0.0001 mg / kg to about 1,000 mg / kg daily.

[0186] In some embodiments, a daily dose range may comprise about 0.01 mg / kg to about 500 mg / kg, or about 0.1 mg / kg to about 200 mg / kg, or about 1 mg / kg to about 100 mg / kg, or about 10 mg / kg to about 50 mg / kg.

[0187] Embodiments of this invention contemplate a dose administered to a patient sufficient to effect a beneficial therapeutic response.

[0188] Determination of dosage may normally be within the skill of a health care practitioner.

[0189] Embodiments of this invention also contemplate various modalities of administration including parenteral, intravenous, infusion, intradermal, subcutaneous, intramuscular, colonical, rectal, and intraperitoneal.

[0190] A therapeutic composition of this invention can be administered in combination with a checkpoint inhibitor, interferon-gamma and an interleukin immunotherapeutic agent for use in treating or ameliorating the symptoms of cancer in a human subject or animal.

[0191] A therapeutic composition of this invention can be administered in combination with other drugs, actives, or agents, as well as standard of care treatments for the same disease, each of which can be administered concurrently, simultaneously, sequentially, or separately in time.

[0192] Examples of diseases contemplated in this invention include a pancreatic cancer, a melanoma, a skin cancer, a lung cancer, a breast cancer, a prostate cancer, a colorectal cancer, a kidney cancer, a stomach cancer, an ovarian cancer, a cervical cancer, a liver cancer, or a multiple myeloma.

[0193] A therapeutic composition of this invention can include pharmaceutically acceptable salt forms, esters, polymorphs or stereoisomers of ingredients, as well as a solvent carrier.

[0194] Examples of a solvent or suspension carrier include sterile water for injection, saline, isotonic saline, and combinations thereof.

[0195] In some embodiments, a deciparticle composition may be stable for at least one hour, or at least one day, or 14 days, or at least 21 days, or at least 28 days in a solvent carrier at 25 °C.

[0196] Numbered embodiments of this invention include the following:

[0197] (1) A deciparticle composition for treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid alkanoyl hydrophobic core.

[0198] (2) A deciparticle composition for use in treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core.

[0199] (3) A method for treating or ameliorating the symptoms of a disease in a subject in need, the method comprising: preparing a deciparticle composition comprising a complex of one or more drugs; an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core; and administering a therapeutically sufficient amount of the deciparticle composition to the subject.

[0200] (4) The composition of any of embodiments 1-3, wherein the deciparticles have an average size of from 4 nm to about 35 nm, or from 4 nm to 20 nm, or from 4 nm to 18 nm.

[0201] (5) The composition of any of embodiments 1-4, wherein the deciparticles have a dispersity of size of up to about 0.1, or up to about 0.2, or up to about 0.3, or up to about 0.4, or up to about 0.5.

[0202] (6) The composition of any of embodiments 1-5, wherein the deciparticles are stable for at least one day stored at 5°C.

[0203] (7) The composition of any of embodiments 1-6, wherein the one or more drugs are poorly water-soluble cancer drugs or antineoplastic drugs.

[0204] (8) The composition of any of embodiments 1-7, wherein the one or more drugs are taxane compounds.

[0205] (9) The composition of any of embodiments 1-8, wherein the one or more drugs are paclitaxel, docetaxel, cabazitaxel, a salt or ester form of any of the foregoing, or a combination thereof.

[0206] (10) The composition of any of embodiments 1-9, wherein the one or more drugs are mTOR kinase inhibitors.

[0207] (11) The composition of any of embodiments 1-10, wherein the one or more drugs are selected from everolimus, rapamycin, ridaforolimus, temsirolimus, umirolimus, zotarolimus, dactolisib, voxtalisib, a salt or ester form of any of the foregoing, and a combination thereof.

[0208] (12) The composition of any of embodiments 1-11, wherein the disease is cancer.

[0209] (13) The composition of any of embodiments 1-12, wherein the disease is a pancreatic cancer, a melanoma, a skin cancer, a lung cancer, a breast cancer, a prostate cancer, a colorectal cancer, a kidney cancer, a stomach cancer, an ovarian cancer, a cervical cancer, a liver cancer, or a multiple myeloma.

[0210] (14) The composition of any of embodiments 1-13, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having weight molecular weight Mw from 350 to 2,500, or 500 to 1,000.

[0211] (15) The composition of any of embodiments 1-14, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having a number molecular weight MN from N=7 to N=56.

[0212] (16) The composition of any of embodiments 1-15, wherein the hydrophobic core is a fatty acid analogue having a branched or unbranched C(3-22) alkyl tail, C(6- 22) alkyl tail, or a branched or unbranched C(6-20) alkenyl tail comprising 1-3 carboncarbon double bonds, and wherein the fatty acid tail is attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

[0213] (17) The composition of any of embodiments 1-16, wherein the hydrophobic core has a log P from 5-7 and weight molecular weight less than 500.

[0214] (18) The composition of any of embodiments 1-17, wherein the amphiphilic compound is selected from mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, mPEG-O-C22, mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG-O(CO)- C15, mPEG-O(CO)-C17, mPEG-O(CO)-C19, mPEG-O(CO)-C21, mPEG-NH(CO)-Cl 1,mPEG-NH(C0)-C13, mPEG-NH(C0)-C15, mPEG-NH(C0)-C17, mPEG-NH(C0)-C19, mPEG-NH(C0)-C21, wherein mPEG has MN with N=12-22, or the amphiphilic molecules have one of the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted alkyl or alkenyl, any of which can be terminated with -CH3, -OH, -COOH, C=O; where PEG can be linked to R1by an O, NH(CO), O(CO); and where PEG can be mPEG with molecular weight from about 340 to about 2,500.

[0215] (19) The composition of any of embodiments 1-18, wherein the amphiphilic compound comprises 60 to 99.9 weight percent of the deciparticle composition.

[0216] (20) The composition of any of embodiments 1-19, wherein the one or more drugs in total comprise 0.1 to 40 weight percent of the deciparticle composition.

[0217] (21) The composition of any of embodiments 1-20, wherein the deciparticle composition is lyophilized to a solid lyophile form.

[0218] (22) The composition of any of embodiments 1-21, wherein the deciparticle composition is reconstituted from a lyophilized form.

[0219] (23) The composition of any of embodiments 1-22, wherein the deciparticle composition is used or administered in combination with a standard of care, cancer chemotherapy, and / or radiation therapy.

[0220] (24) The composition of any of embodiments 1-23, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from an antimetabolite drug, an alkylating drug, and a targeted cancer drug.

[0221] (25) The composition of any of embodiments 1-24, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from gemcitabine, temozolamide, bevacizumab, 5 -fluorouracil (antimetabolite drugs), cyclophosphamide, busulfan (alkylating drugs), a targeted monoclonal antibody cancer drug, an immune checkpoint inhibitor, and a tyrosine kinase receptor inhibitor.

[0222] (26) The composition of any of embodiments 1-25, wherein the maximum solution concentration for administration of the deciparticle composition is from 5-50 mg / mL.

[0223] (27) The composition of any of embodiments 1-26, wherein the maximum tolerated dose of the deciparticle composition is 500 mg / kg.

[0224] (28) A composition, comprising: a pharmaceutically acceptable suspension of the deciparticle composition of any of claims 1-3 in a solvent; and one or more cryoprotective compounds.

[0225] (29) The composition of embodiment 28, wherein the one or more cryoprotective compounds is a dextrin compound, or a saccharide sugar compound, or a combination thereof.

[0226] (30) The composition of embodiment 28 or 29, wherein the total amount of the cryoprotective compounds is from 1% to 40% (w / v) of the composition, or from 1% to 25% (w / v) of the composition.

[0227] (31) A compound, comprising an amphiphilic molecule having one of the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted (C6- 22)alkyl, (C6-22)alkoxy or (C6-22)alkenyl, where R2is terminated with -H, -CH3, -OH, -COOH, C=O; wherein PEG is linked to R1by an O, NH(CO), O(CO); wherein PEG has molecular weight from about 300 to about 2,500.

[0228] (32) The compound of embodiment 31, wherein PEG is mPEG with molecular weight from about 340 to about 2,500.

[0229] (33) The compound of embodiment 31 or 32, wherein the amphiphilic molecule is mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, or mPEG-O-C22, wherein mPEG has molecular weight from about 340 to about 2,500.

[0230] (34) The compound of any of embodiments 31-33, comprising mPEG-O-C18, wherein mPEG has molecular weight 550.

[0231] (35) The compound of any of embodiments 31-34, comprising mPEG-O(CO)- Cl l, mPEG-O(CO)-C13, mPEG-O(CO)-Cl 5, mPEG-O(CO)-C17, mPEG-O(CO)-C19, or mPEG-O(CO)-C21, wherein mPEG has molecular weight from about 340 to about 2,500.

[0232] (36) The compound of any of embodiments 31-35, comprising mPEG-O(CO)- C17, wherein mPEG has molecular weight 550.

[0233] (37) The compound of any of embodiments 31-36, comprising mPEG- NH(CO)-C11, mPEG-NH(CO)-C13, mPEG-NH(CO)-C15, mPEG-NH(CO)-C17, mPEG- NH(CO)-C19, or mPEG-NH(CO)-C21, wherein mPEG has molecular weight from about 340 to about 2,500.

[0234] (38) The compound of any of embodiments 31-37, comprising mPEG- NH(CO)-C17, wherein mPEG has molecular weight 550.

[0235] (39) A method for making a deciparticle composition of any of embodiments 1-30, the method comprising: mixing the one or more drugs in an organic solvent; contacting the amphiphilic compound with the drugs in the organic solvent; mixing or vortexing the organic solvent; filtering the deciparticle composition in the organic solvent to remove particles or aggregates larger than 15 nm, or 30 nm, or 75 nm, or 100 nm; and removing residual organic solvent and / or free drug from the deciparticle composition.

[0236] (40) A deciparticle composition made by the method of embodiment 39.

[0237] All publications including patents, patent application publications, and nonpatent publications referred to in this description, as well as the sequence listing are each expressly incorporated herein by reference in their entirety for all purposes.

[0238] Although the foregoing disclosure has been described in detail by way of example for purposes of clarity of understanding, it will be apparent to the artisan that certain changes and modifications are comprehended by the disclosure and may be practiced without undue experimentation within the scope of the appended claims, which are presented by way of illustration not limitation. This invention includes all such additional embodiments, equivalents, and modifications. This invention includes any combinations or mixtures of the features, materials, elements, or limitations of the various illustrative components, examples, and claimed embodiments.

[0239] It is emphasized herein according to common practice the features of the drawings have arbitrary scale and are intended to cover similar features that may be arbitrarily expanded or reduced.EXAMPLES

[0240] Deciparticle characteristics were determined using a ZETASIZER 3600 (Malvern). Typically, 20 pL of a sample was diluted with 280 pL of DI water, resulting in a minimum final volume of 300 pL in a quartz cuvette. Three readings were typically taken for each sample. Data provided can be Z-average mean particle size, volume mean average size of particles based on volume distribution within the sample, and poly dispersity index (PDI).

[0241] Example 1. Deciparticle compositions made with amphiphilic molecules complexed with paclitaxel. The number of carbon atoms of the hydrophobic core moiety of the amphiphilic molecule conjugate was shown to influence the particle size of deciparticles made with the amphiphilic molecules and paclitaxel. FIG. 1 shows a plot of the observed sizes of some deciparticles composed of an amphiphilic molecule complexed with paclitaxel shown in Examples 6-14 herein. The results are consistent with particle sizes of deciparticles made with the amphiphilic molecules complexed with everolimus in Examples 2-5.

[0242] Example 2. Deciparticle compositions made with mPEG(550)-O-C12 and everolimus (CAS 159351-69-6).

[0243] Deciparticles were formed using a modified dry film method. 20 mg of amphiphilic molecule mPEG(550)-O-C 12 was dissolved in 1 mL of acetone (20 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block. 2.11 mg everolimus drug was dissolved in 1 mL acetone (2 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0244] 500 pL of the amphiphilic molecule solution was mixed with 500 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0245] The thin film was hydrated in 500 pL of 60°C water and vortexed for 10 s. 100 pL of the hydrated thin film was diluted with 200 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0246] The average particle size of deciparticle compositions made with mPEG(550)-NH(CO)-(CH2)3CO2H and paclitaxel was 9.3 nm. FIG. 3 shows the measured particle size distribution for this deciparticle composition.

[0247] Example s. Deciparticle compositions made with mPEG(550)-NH(CO)-C17 and everolimus.

[0248] Deciparticles were formed using a modified dry film method. 20 mg of amphiphilic molecule mPEG(550)-NH(CO)-C17 was dissolved in 1 mL of acetone (20 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block. 2.11 mg everolimus drug was dissolved in 1 mL acetone (2 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0249] 500 pL of the amphiphilic molecule solution was mixed with 500 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0250] The thin film was hydrated in 500 pL of 60°C water and vortexed for 10 s. 100 pL of the hydrated thin film was diluted with 200 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0251] The average particle size of deciparticle compositions made with mPEG(550)-NH(CO)-C17 and paclitaxel was 8.9 nm. FIG. 4 shows the measured particle size distribution for this deciparticle composition.

[0252] Example 4. Deciparticle compositions made with mPEG(550)-O(CO)-(CH2)2CO2H and everolimus.

[0253] Deciparticles were formed using a modified dry film method. 20 mg of amphiphilic molecule mPEG(550)-O(CO)-(CH2)2CO2H was dissolved in 1 mL of acetone (20 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block. 2.11 mg everolimus drug was dissolved in 1 mL acetone (2 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0254] 500 pL of the amphiphilic molecule solution was mixed with 500 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C.Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0255] The thin film was hydrated in 500 pL of 60°C water and vortexed for 10 s. 100 pL of the hydrated thin film was diluted with 200 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0256] The average particle size of deciparticle compositions made with mPEG(550)- O(CO)-(CH2)2CO2H and everolimus was 1.3 nm. FIG. 5 shows the measured particle size distribution for this deciparticle composition.

[0257] Example 5. Deciparticle compositions made with mPEG(550)-O(CO)-(CH2)3CO2H and everolimus.

[0258] Deciparticles were formed using a modified dry film method. 20 mg of amphiphilic molecule mPEG(550)-O(CO)-(CH2)3CO2H was dissolved in 1 mL of acetone (20 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block. 2.11 mg everolimus drug was dissolved in 1 mL acetone (2 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0259] 500 pL of the amphiphilic molecule solution was mixed with 500 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0260] The thin film was hydrated in 500 pL of 60°C water and vortexed for 10 s. 100 pL of the hydrated thin film was diluted with 200 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0261] The average particle size of deciparticle compositions made with mPEG(550)- O(CO)-(CH2)3CO2H and everolimus was 1.1 nm. FIG. 6 shows the measured particle size distribution for this deciparticle composition.

[0262] Example 6. Deciparticle compositions made with mPEG(550)-O-C12 and paclitaxel (CAS 33069-62-4).

[0263] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-O-C12 was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0264] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0265] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette.DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0266] The average particle size of deciparticle compositions made with mPEG(550)- O-C12 and paclitaxel was 8.0 nm. FIG. 7 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-O-C12 and paclitaxel.

[0267] Example 7. Deciparticle compositions made with mPEG(550)-NH(CO)-C17 and paclitaxel.

[0268] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-NH(CO)-C17 was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0269] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0270] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette.DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle sizewas calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0271] The average particle size of deciparticle compositions made with mPEG(550)- NH(CO)-C17 and paclitaxel was 10.2 nm. FIG. 8 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-NH(CO)- C17 and paclitaxel.

[0272] Example 8. Deciparticle compositions made with mPEG(550)-NH(CO)-(CH2)2CO2H and paclitaxel.

[0273] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-NH(CO)-(CH2)2CO2H was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0274] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0275] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0276] The average particle size of deciparticle compositions made with mPEG(550)- NH(CO)-(CH2)2CO2H and paclitaxel was 1.0 nm. FIG. 9 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-NH(CO)- (CH2)2CO2H and paclitaxel.

[0277] Example 9. Deciparticle compositions made with mPEG(550)-O(CO)-(CH2)2CO2H and paclitaxel.

[0278] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-O(CO)-(CH2)2CO2H was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0279] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0280] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0281] The average particle size of deciparticle compositions made with mPEG(550)- O(CO)-(CH2)2CO2H and paclitaxel was 1.3 nm. FIG. 10 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-O(CO)- (CH2)2CO2H and paclitaxel.

[0282] Example 10. Deciparticle compositions made with mPEG(550)-O(CO)-(CH2)3CO2H and paclitaxel.

[0283] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-O(CO)-(CH2)3CO2H was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0284] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0285] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0286] The average particle size of deciparticle compositions made with mPEG(550)- O(CO)-(CH2)3CO2H and paclitaxel was 1.2 nm. FIG. 11 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-O(CO)- (CH2)3CO2H and paclitaxel.

[0287] Example 11. Deciparticle compositions made with mPEG(550)-NH(CO)- (CH2)3CO2H and paclitaxel.

[0288] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-NH(CO)-(CH2)3CO2H was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0289] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0290] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0291] The average particle size of deciparticle compositions made with mPEG(550)- NH(CO)-(CH2)3CO2H and paclitaxel was 1.0 nm. FIG. 12 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-NH(CO)- (CH2)3CO2H and paclitaxel.

[0292] Example 12. Deciparticle compositions made with mPEG(550)-NH(CO)-Cl 1 and paclitaxel.

[0293] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-NH(CO)-Cl 1 was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0294] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0295] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0296] The average particle size of deciparticle compositions made with mPEG(550)- NH(CO)-C11 and paclitaxel was 8.2 nm. FIG. 13 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-NH(CO)- C11 and paclitaxel.

[0297] Example 13. Deciparticle compositions made with mPEG(550)-NH(CO)-C15 and paclitaxel.

[0298] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-NH(CO)-C15 was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0299] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0300] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0301] The average particle size of deciparticle compositions made with mPEG(550)- NH(CO)-C15 and paclitaxel was 9.2 nm. FIG. 14 shows deciparticle size anddistribution measured for deciparticle compositions made with mPEG(550)-NH(CO)- C15 and paclitaxel.

[0302] Example 14. Deciparticle compositions made with mPEG(550)-O-C18 and paclitaxel.

[0303] Deciparticles were formed using a modified dry film method. 15 mg of amphiphilic molecule mPEG(550)-O-C18 was dissolved in 1 mL of acetone. The solution was vortexed for 10 s, then raised to 60°C on a heat block. 30 mg paclitaxel drug was dissolved in 3 mL acetone (10 mg / ml). The solution was vortexed for 10 s, then raised to 60°C on a heat block.

[0304] 100 pL of the amphiphilic molecule solution was mixed with 15 pL of paclitaxel solution and vortexed for 10 s. Temperature was maintained at 60°C. Acetone was evaporated off with blowing air over the drug / amphiphilic molecule solution for 3-5 minutes to form a thin film containing deciparticles.

[0305] The thin film was hydrated in 75 pL of 60°C water and vortexed for 10 s. 25 pL of the hydrated thin film was diluted with 275 pL of DI water in a glass cuvette. DLS analysis was obtained in triplicate using a ZETASIZER (Malvern). Particle size was calculated by volume analysis at 37°C. Samples were stored at 5°C for 24 hr, and re-analyzed. No change in particle size was observed.

[0306] The average particle size of deciparticle compositions made with mPEG(550)- O-C18 and paclitaxel was 9.8 nm. FIG. 15 shows deciparticle size and distribution measured for deciparticle compositions made with mPEG(550)-O-C18 and paclitaxel.

[0307] Example 15. Lyophilization of pharmaceutically acceptable suspensions of deciparticle compositions.

[0308] To a pharmaceutically acceptable suspension of a deciparticle composition is added sucrose and cyclodextrin at about pH 7.0. An aliquot of suspension is added to a glass vial in a metal pan. The vial is cooled at -20°C overnight, then transferred to a lyophilization apparatus. Vacuum is applied while maintaining the temperature at - 20°C for at least 4 hours. Under vacuum, the temperature is slowly raised to -10°C for at least 4 hours. Under vacuum, the temperature is slowly raised to 4°C for at least 2 hours, then to ambient room temperature for at least 2 hours. The vial is sealed under inert atmosphere.

Claims

WHAT IS CLAIMED IS:

1. A deciparticle composition for treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more poorly water-soluble cancer drugs or antineoplastic drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid alkanoyl hydrophobic core.

2. A deciparticle composition for use in treating or ameliorating the symptoms of a disease in a subject, the composition comprising a complex of one or more drugs; and an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core.

3. A method for treating or ameliorating the symptoms of a disease in a subject in need, the method comprising: preparing a deciparticle composition comprising a complex of one or more drugs; an amphiphilic compound comprising a polyethylene glycol hydrophilic oligomer and a fatty acid analogue hydrophobic core; and administering a therapeutically sufficient amount of the deciparticle composition to the subject.

4. The composition of any of claims 1-3, wherein the deciparticles have an average size of from 4 nm to about 35 nm, or from 4 nm to 20 nm, or from 4 nm to 18 nm.

5. The composition of any of claims 1-3, wherein the deciparticles have a dispersity of size of up to about 0.1, or up to about 0.2, or up to about 0.3, or up to about 0.4, or up to about 0.5.

6. The composition of any of claims 1-3, wherein the deciparticles are stable for at least one day stored at 5 °C.

7. The composition of any of claims 1-3, wherein the one or more drugs are poorly water- soluble cancer drugs or antineoplastic drugs.

8. The composition of any of claims 1-3, wherein the one or more drugs are taxane compounds.

9. The composition of any of claims 1-3, wherein the one or more drugs are paclitaxel, docetaxel, cabazitaxel, a salt or ester form of any of the foregoing, or a combination thereof.

10. The composition of any of claims 1-3, wherein the one or more drugs are mTOR kinase inhibitors.

11. The composition of any of claims 1-3, wherein the one or more drugs are selected from everolimus, rapamycin, ridaforolimus, temsirolimus, umirolimus, zotarolimus, dactolisib, voxtalisib, a salt or ester form of any of the foregoing, and a combination thereof.

12. The composition of any of claims 1-3, wherein the disease is cancer.

13. The composition of any of claims 1-3, wherein the disease is a pancreatic cancer, a melanoma, a skin cancer, a lung cancer, a breast cancer, a prostate cancer, a colorectal cancer, a kidney cancer, a stomach cancer, an ovarian cancer, a cervical cancer, a liver cancer, or a multiple myeloma.

14. The composition of any of claims 1-3, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having weight molecular weight Mw from 350 to 2,500, or 500 to 1,000.

15. The composition of any of claims 1-3, wherein the hydrophilic oligomer is a polyethylene glycol or mPEG having a number molecular weight MN from N=7 to N=56.

16. The composition of any of claims 1-3, wherein the hydrophobic core is a fatty acid analogue having a branched or unbranched C(3-22) alkyl tail, C(6-22) alkyl tail, or a branched or unbranched C(6-20) alkenyl tail comprising 1-3 carbon-carbon double bonds, and wherein the fatty acid tail is attached to the hydrophilic oligomer by an ester, ether, or amide linkage.

17. The composition of any of claims 1-3, wherein the hydrophobic core has a log P from 5-7 and weight molecular weight less than 500.

18. The composition of any of claims 1-3, wherein the amphiphilic compound is selected from mPEG-O-C12, mPEG-O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, mPEG-O- C22, mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG-O(CO)-C15, mPEG-O(CO)-C17, mPEG- O(CO)-C19, mPEG-O(CO)-C21, mPEG-NH(CO)-Cl 1, mPEG-NH(CO)-C13, mPEG-NH(CO)- C15, mPEG-NH(CO)-C17, mPEG-NH(CO)-C19, mPEG-NH(CO)-C21, wherein mPEG has MNwith N= 12-22, or the amphiphilic molecules have one of the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted alkyl or alkenyl, any of which can be terminated with -CEE, -OH, -COOH, C=O;where PEG can be linked to R1by an 0, NH(CO), O(CO); and where PEG can be mPEG with molecular weight from about 340 to about 2,500.

19. The composition of any of claims 1-3, wherein the amphiphilic compound comprises 60 to 99.9 weight percent of the deciparticle composition.

20. The composition of any of claims 1-3, wherein the one or more drugs in total comprise 0.1 to 40 weight percent of the deciparticle composition.

21. The composition of any of claims 1-3, wherein the deciparticle composition is lyophilized to a solid lyophile form.

22. The composition of any of claims 1-3, wherein the deciparticle composition is reconstituted from a lyophilized form.

23. The composition of any of claims 1-3, wherein the deciparticle composition is used or administered in combination with a standard of care, cancer chemotherapy, and / or radiation therapy.

24. The composition of any of claims 1-3, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from an antimetabolite drug, an alkylating drug, and a targeted cancer drug.

25. The composition of any of claims 1-3, wherein the deciparticle composition is used or administered in combination with a cancer drug selected from gemcitabine, temozolamide, bevacizumab, 5 -fluorouracil (antimetabolite drugs), cyclophosphamide, busulfan (alkylating drugs), a targeted monoclonal antibody cancer drug, an immune checkpoint inhibitor, and a tyrosine kinase receptor inhibitor.

26. The composition of any of claims 1-3, wherein the maximum solution concentration for administration of the deciparticle composition is from 5-50 mg / mL.

27. The composition of any of claims 1-3, wherein the maximum tolerated dose of the deciparticle composition is 500 mg / kg.

28. A composition, comprising: a pharmaceutically acceptable suspension of the deciparticle composition of any of claims 1-3 in a solvent; and one or more cryoprotective compounds.

29. The composition of claim 28, wherein the one or more cryoprotective compounds is a dextrin compound, or a saccharide sugar compound, or a combination thereof.

30. The composition of claim 28, wherein the total amount of the cryoprotective compounds is from 1% to 40% (w / v) of the composition, or from 1% to 25% (w / v) of the composition.

31. A compound, comprising an amphiphilic molecule having one of the following structures:PEG-R1, Formula I, where R1is substituted or unsubstituted alkyl, alkenyl, cycloalkyl, or alkoxy;PEG-(CO)R2, Formula II, where R2is substituted or unsubstituted (C6-22)alkyl, (C6- 22)alkoxy or (C6-22)alkenyl, where R2is terminated with -H, -CEE, -OH, -COOH, C=O; wherein PEG is linked to R1by an O, NH(CO), O(CO); wherein PEG has molecular weight from about 300 to about 2,500.

32. The compound of claim 31, wherein PEG is mPEG with molecular weight from about 340 to about 2,500.

33. The compound of claim 31, wherein the amphiphilic molecule is mPEG-O-C12, mPEG- O-C14, mPEG-O-C16, mPEG-O-C18, mPEG-O-C20, or mPEG-O-C22, wherein mPEG has molecular weight from about 340 to about 2,500.

34. The compound of claim 31, comprising mPEG-O-C18, wherein mPEG has molecular weight 550.

35. The compound of claim 31, comprising mPEG-O(CO)-Cl 1, mPEG-O(CO)-C13, mPEG- O(CO)-C15, mPEG-O(CO)-C17, mPEG-O(CO)-C19, or mPEG-O(CO)-C21, wherein mPEG has molecular weight from about 340 to about 2,500.

36. The compound of claim 31, comprising mPEG-O(CO)-C17, wherein mPEG has molecular weight 550.

37. The compound of claim 31, comprising mPEG-NH(CO)-Cl 1, mPEG-NH(CO)-C13, mPEG-NH(CO)-C15, mPEG-NH(CO)-C17, mPEG-NH(CO)-C19, or mPEG-NH(CO)-C21, wherein mPEG has molecular weight from about 340 to about 2,500.

38. The compound of claim 31, comprising mPEG-NH(CO)-C17, wherein mPEG has molecular weight 550.

39. A method for making a deciparticle composition of any of claims 1-3, the method comprising: mixing the one or more drugs in an organic solvent; contacting the amphiphilic compound with the drugs in the organic solvent; mixing or vortexing the organic solvent; filtering the deciparticle composition in the organic solvent to remove particles or aggregates larger than 15 nm, or 30 nm, or 75 nm, or 100 nm; and removing residual organic solvent and / or free drug from the deciparticle composition.

40. A deciparticle composition made by the method of claim 39.

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