Amphiphile-Polymer Particles

Abstract

This invention relates to amphiphile-polymer particles, compositions, methods of making, and methods of use thereof.

What is claimed is: 
     
         1 . A particle comprising:
 a water-insoluble polymeric core; and   a payload and a first amphiphile within the core.   
     
     
         2 . The particle of  claim 1 , further comprising a shell comprising a second amphiphile surrounding the water-insoluble polymeric core. 
     
     
         3 . A particle prepared by a process comprising:
 obtaining a first solution comprising a water-insoluble polymer, a payload and a first amphiphile in a water-miscible solvent;   mixing the first solution with an aqueous second solution to form an aqueous composition comprising a particle comprising a water-insoluble polymeric core comprising the water-insoluble polymer; the payload; and the first amphiphile.   
     
     
         4 . The particle of  claim 3 , wherein the process further comprises mixing the aqueous composition with a solution comprising a second amphiphile to form a shell surrounding the core. 
     
     
         5 . The particle of any one of  claims 1 - 4 , wherein the payload and the first amphiphile have complementary electrical charges. 
     
     
         6 . The particle of any one of  claims 1 - 5 , wherein the water-insoluble polymeric core comprises one or more polymers selected from polyethylene glycol, poly(ethylene glycol)-co-poly(D,L-lactic acid), poly(ethylene glycol)-co-(poly(lactide-co-glycolide)), polystyrene-b-polyethylene oxide, polybutylacrylate-b-polyacrylic acid, polybutylmethacrylate-b-polyethyleneoxidepolyethylene oxide, polyethyleneimine, diethyleneglycol, triethyleneglycol, polyalkylene glycol, polyalkyline oxide, polyvinyl alcoholpolyvinylpyrrolidone, polyvinylmethylether, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyl-oxazoline, polyhydroxypropylmethacrylamide, polymethacrylamide, polydimethylacryl-amide, polyhydroxypropylmethacrylate, polyhydroxyethylacrylate, hydroxymethylcellulose, hydroxyethylcellulose, polyglycerine, polyaspartamide, polyoxyethlene-polyoxypropylene copolymer (poloxamer), poly(acrylic acid), poly(methacrylic acid), poly(itaconic acid), poly(maleic acid), polyoxyethylenes, polyethyleneoxide, polylactic acid, polypropylene oxide, poly(lactide-co-glycolide), poly(epsilon-caprolactone), poly(ethylethylene), polybutadiene, polyglycolide, polymethylacrylate, polyvinylbutylether, polystyrene, polycyclopentadienylmethylnorbornene, polyethylenepropylene, polyethylethylene, polyisobutylene, polysiloxane, poly(methyl acrylate), poly(ethyl acrylate), poly(propyl acrylate), poly(n-butyl acrylate), poly(isobutyl acrylate), poly(2-ethyl acrylate), poly(t-butyl acrylate), poly(ethyl methacrylate), poly(n-butyl methacrylate), poly(isobutyl methacrylate), poly(acrylonitriles), poly(methacrylonitrile), poly(vinyl acetate), poly(vinylversatate), poly(vinylpropionate), poly(vinylformamide), poly(vinylacetamide), poly(vinylpyridines), poly(vinyllimidazole), poly(aminoalkylacrylates), poly(aminoalkylsmethacrylates), poly(aminoalkyl(meth)acrylamides), fluorescent polymers, and polystyrenes. 
     
     
         7 . The particle any one of  claims 1 - 5 , wherein the water-insoluble polymeric core comprises one or more polymers selected from poly(glycolic acid); poly(lactic acid); poly(caprolactone); poly(lactide-co-glycolide); poly(ortho ester) II; poly(alkyl cyanoacrylate); desaminotyrosyl octyl ester; polyphosphoesters; polyester amides; polyurethanes; chitosan; acrylates copolymer; acrylic acid-isooctyl acrylate copolymer; ammonio methacrylate copolymer; ammonio methacrylate copolymer type A; ammonio methacrylate copolymer type B; butyl ester of vinyl methyl ether/maleic anhydride copolymer (125,000 molecular weight); carbomer homopolymer type A (allyl pentaerythritol crosslinked); carbomer homopolymer type B (allyl sucrose crosslinked); cellulosic polymers; dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymer; dimethylsiloxane/methylvinylsiloxane copolymer; divinylbenzene styrene copolymer; ethyl acrylate-methacrylic acid copolymer; ethyl acrylate and methyl methacrylate copolymer (2:1; 750,000 molecular weight); ethylene vinyl acetate copolymer; ethylene-propylene copolymer; ethylene-vinyl acetate copolymer (28% vinyl acetate); glycerin polymer solution i-137; glycerin polymer solution im-137; hydrogel polymer; ink/polyethylene terephthalate/aluminum/polyethylene/sodium polymethacrylate/ethylene vinyl acetate copolymer; isooctyl acrylate/acrylamide/vinyl acetate copolymer; Kollidon® VA 64 polymer; methacrylic acid-ethyl acrylate copolymer (1:1) type A; methacrylic acid-methyl methacrylate copolymer (1:1); methacrylic acid-methyl methacrylate copolymer (1:2); methacrylic acid copolymer; methacrylic acid copolymer type A; methacrylic acid copolymer type B; methacrylic acid copolymer type C; octadecene-1/maleic acid copolymer; PEG-22 methyl ether/dodecyl glycol copolymer; PEG-45/dodecyl glycol copolymer; Polyester polyamine copolymer; poly(ethylene glycol) 1,000; poly(ethylene glycol) 1,450; poly(ethylene glycol) 1,500; poly(ethylene glycol) 1,540; poly(ethylene glycol) 200; poly(ethylene glycol) 20,000; poly(ethylene glycol) 200,000; poly(ethylene glycol) 2,000,000; poly(ethylene glycol) 300; poly(ethylene glycol) 300-1,600; poly(ethylene glycol) 300-1,600; poly(ethylene glycol) 3,350; poly(ethylene glycol) 3,500; poly(ethylene glycol) 400; poly(ethylene glycol) 4,000; poly(ethylene glycol) 4,500; poly(ethylene glycol) 540; poly(ethylene glycol) 600; poly(ethylene glycol) 6,000; poly(ethylene glycol) 7,000; poly(ethylene glycol) 7,000,000; poly(ethylene glycol) 800; poly(ethylene glycol) 8,000; poly(ethylene glycol) 900; polyvinyl chloride-polyvinyl acetate copolymer; povidone acrylate copolymer; povidone/eicosene copolymer; polyoxy(methyl-1,2-ethanediyl), alpha-hydro-omega-hydroxy-, polymer with 1,1′-methylenebis[4-isocyanatocyclohexane] copolymer; polyvinyl methyl ether/maleic acid copolymer; styrene/isoprene/styrene block copolymer; vinyl acetate-crotonic acid copolymer; {poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)]}, and {poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]}. 
     
     
         8 . The particle of  claim 7 , wherein the water-insoluble polymeric core comprises {poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)]}. 
     
     
         9 . The particle of  claim 7 , wherein the water-insoluble polymeric core comprises {poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]}. 
     
     
         10 . The particle of any one of  claims 1 - 5 , wherein the water-insoluble polymeric core comprises one or more polymers selected from polylactic acids, polyglycolic acids, and copolymers of lactic acid and glycolic acid. 
     
     
         11 . The particle of  claim 10 , wherein the water-insoluble polymeric core comprises one or more copolymers of lactic acid and glycolic acid. 
     
     
         12 . The particle of  claim 11 , comprising a copolymer of lactic acid and glycolic acid that comprises lactic acid and glycolic acid monomer units in a ratio of about 1:1. 
     
     
         13 . The particle of any one of  claims 1 - 12 , wherein the first amphiphile is cationic. 
     
     
         14 . The particle of any one of  claims 1 - 12 , wherein the first amphiphile is anionic. 
     
     
         15 . The particle of any one of  claims 1 - 12 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: lecithin, amino dendrimers, PEG-phospholipids, PEG-ceramides, anionic lipids, and cationic lipids. 
     
     
         16 . The particle of  claim 15 , wherein the first amphiphile comprises an amino dendrimer. 
     
     
         17 . The particle of  claim 15 , wherein the first amphiphile comprises a cationic lipid. 
     
     
         18 . The particle of any one of  claims 1 - 12 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: lecithin; G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-di stearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]); N-octanoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)2000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)2000]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)5000]}; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane; 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine; 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; 1,2-distearoyl-sn-glycero-3-ethylphosphocholine; 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine; 1,2-di-O-tetradecyl-sn-glycero-3-phospho-(1′-rac-glycerol); and 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1′-sn-glycerol). 
     
     
         19 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane. 
     
     
         20 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises G0-C14 dendrimer. 
     
     
         21 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises polypropylenimine tetramine dendrimer, generation 1. 
     
     
         22 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises ethylenediamine branched polyethylenimine. 
     
     
         23 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises 1,2-dioleoyl-3-trimethylammonium-propane. 
     
     
         24 . The particle of any one of  claims 1 - 13 , wherein the first amphiphile comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane. 
     
     
         25 . The particle of any one of  claims 1 - 24 , wherein the water-insoluble core comprises the first amphiphile in an amount from about 1% to about 50% by weight. 
     
     
         26 . The particle of  claim 25 , wherein the water-insoluble core comprises the first amphiphile in an amount from about 10% to about 20% by weight. 
     
     
         27 . The particle of any one of  claims 1 - 26 , wherein the payload comprises a small molecule. 
     
     
         28 . The particle of any one of  claims 1 - 26 , wherein the payload comprises a biomolecule. 
     
     
         29 . The particle of any one of  claims 1 - 28 , wherein the payload is anionic. 
     
     
         30 . The particle of any one of  claims 1 - 28 , wherein the payload is cationic. 
     
     
         31 . The particle of any one of  claims 1 - 30 , wherein the payload comprises one or more species selected from the group consisting of: polypeptides; proteins; nucleic acids; polypeptide hormones; antibody-drug conjugates; antibody fragment-drug conjugates; protein-drug conjugates; peptide-drug conjugates; fusion proteins; enzymes; monoclonal antibodies; bispecific monoclonal antibodies; and multimeric fusion proteins. 
     
     
         32 . The particle of  claim 31 , wherein the payload comprises a protein. 
     
     
         33 . The particle of  claim 32 , wherein the payload is enhanced green fluorescent protein. 
     
     
         34 . The particle of any one of  claims 1 - 30 , wherein the payload comprises one or more species selected from the group consisting of: transforming growth factor-beta, interferons, colony stimulating factors, granulocyte colony stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17, interleukin-18, interleukin-22, interleukin-23, interleukin-35, atacicept, abatacept, alefacept, etanercept, romiplostim, rilonacept, adalimumab, alemtuzumab, atlizumab, canakinumab, certolizumab, certolizumab pegol, daclizumab, efalizumab, fontolizumab, golimumab, infliximab, mepolizumab, natalizumab, omalizumab, ruplizumab, ustekinumab, visilizumab, zanolimumab, vedolizumab, belimumab, otelixizumab, teplizumab, rituximab, ofatumumab, ocrelizumab, epratuzumab, eculizumab, and briakinumab. 
     
     
         35 . The particle of any one of  claims 1 - 30 , wherein the payload comprises one or more species selected from the group consisting of: abagovomab, adecatumumab, afutuzumab, alacizumab pegol, altumomab pentetate, amatuximab, anatumomab mafenatox, apolizumab, arcitumomab, bavituximab, bectumomab, belimumab, bevacizumab, bivatuzumab mertansine, blinatumomab, brentuximab vedotin, cantuzumab mertansine, cantuzumab ravtansine, capromab pendetide, cetuximab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, dacetuzumab, demcizumab, detumomab, drozitumab, ecromeximab, eculizumab, elotuzumab, ensituximab, epratuzumab, etaracizumab, farletuzumab, figitumumab, flanvotumab, galiximab, gemtuzumab ozogamicin, girentuximab, ibritumomab tiuxetan, imgatuzumab, ipilimumab, labetuzumab, lexatumumab, lorvotuzumab mertansine, nimotuzumab, ofatumumab, oregovomab, panitumumab, pemtumomab, pertuzumab, tacatuzumab tetraxetan, tositumomab, trastuzumab, totumumab, and zalutumumab. 
     
     
         36 . The particle of any one of  claims 1 - 30 , wherein the payload comprises one or more species selected from the group consisting of: agalsidase beta, imiglucerase, velaglucerase alfa, taliglucerase, alglucosidase alfa, laronidase, idursulfase, and galsulfase. 
     
     
         37 . The particle of any one of  claims 1 - 30 , wherein the payload comprises a nucleic acid. 
     
     
         38 . The particle of  claim 37 , wherein the nucleic acid is double stranded. 
     
     
         39 . The particle of  claim 37 , wherein the nucleic acid is single stranded. 
     
     
         40 . The particle of any one of  claims 37 - 39 , wherein the nucleic acid comprises a vector. 
     
     
         41 . The particle of  claim 40 , wherein the vector comprises at least one selected from a plasmid and a viral vector. 
     
     
         42 . The particle of  claim 41 , wherein the viral vector comprises one or more vectors selected from the group consisting of retroviral vectors, lentiviral vectors, adenoviral vectors, and adeno-associated viral vectors. 
     
     
         43 . The particle of  claim 37 , wherein the nucleic acid is a DNA. 
     
     
         44 . The particle of  claim 37 , wherein the nucleic acid is an RNA. 
     
     
         45 . The particle of  claim 44 , wherein the nucleic acid is selected from the group consisting of siRNAs, microRNAs, and mRNAs. 
     
     
         46 . The particle of  claim 45 , wherein the nucleic acid is siRNA. 
     
     
         47 . The particle of  claim 45 , wherein siRNA is selected from the group consisting of siPHB1, siMYC, si-c-MYC, siBRAF, and siBRAF V600E . 
     
     
         48 . The particle of  claim 45 , wherein the nucleic acid is microRNA. 
     
     
         49 . The particle of  claim 45 , wherein the nucleic acid is mRNA. 
     
     
         50 . The particle of  claim 37 , wherein the nucleic acid decreases expression of a protein selected from kinesin spindle protein, RRM2, keratin 6a, HER1, ErbB2, VEGFR1, VEGFR3), PDGFR-α, PDGFR-β, EGFR, FGFR1, FGFR2, FGFR3, FGFR4, EphA2, EphA3, EphA4, HER2, HER3, HER4, INS-R, IGF-1R, IR-R, CSF1R, KIT, FLK-II, KDR/FLK-1, FLK-4, flt-1, c-Met, Ron, Sea, TRKA, TRKB, TRKC, FLT3, VEGFR/Flt2, Flt4, EphA1, EphB2, EphB4, Pim1, Pim2, Pim3, Tie2PKN3, PLK1, PLK2, PLK3, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, Abl, Kit, KDR, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAP kinase, PI3K, Akt1, Akt2, Akt3, TGF-βR, KRAS, BRAF, CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK9, GSK3, CLK1, CLK4, Aurora A, Aurora B, Aurora C, MEK1, MEK2, mTOR, protein kinase A, protein kinase C, protein kinase G, and PHB1. 
     
     
         51 . The particle of  claim 37 , wherein the nucleic acid decreases expression of a protein selected from kinesin spindle protein, RRM2, keratin 6a, HER1, ErbB2, VEGFR1, VEGFR3), PDGFR-α, PDGFR-β, EGFR, FGFR1, FGFR2, FGFR3, FGFR4, EphA2, EphA3, EphA4, HER2, HER3, HER4, INS-R, IGF-1R, IR-R, CSF1R, KIT, FLK-II, KDR/FLK-1, FLK-4, flt-1, c-Met, Ron, Sea, TRKA, TRKB, TRKC, FLT3, VEGFR/Flt2, Flt4, EphA1, EphB2, EphB4, Pim1, Pim2, Pim3, Tie2PKN3, PLK1, PLK2, PLK3, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, Abl, Kit, KDR, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAP kinase, PI3K, Akt1, Akt2, Akt3, TGF-βR, KRAS, BRAF, BRAF V600E , CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK9, GSK3, CLK1, CLK4, Aurora A, Aurora B, Aurora C, MEK1, MEK2, mTOR, protein kinase A, protein kinase C, siMYC, si-c-MYC, protein kinase G, and PHB1. 
     
     
         52 . The particle of  claim 37 , wherein the nucleic acid decreases expression of a viral region selected from the group consisting of: L segments, M segments, and S segments. 
     
     
         53 . The particle of any one of  claims 1 - 52 , wherein the second amphiphile comprises one or more compounds selected from neutral lipids, amino dendrimers, PEG-phospholipids, PEG-ceramides, anionic lipids, and cationic lipids. 
     
     
         54 . The particle of  claim 53 , wherein the second amphiphile comprises one or more selected from the group consisting of: lecithin; 1,2-dioctanoyl-sn-glycerol; 1,2-didecanoyl-sn-glycerol; D-erythro-sphingosine; D-glucosyl-β-1,1′ N-octanoyl-D-erythro-sphingosine; N-butyroyl-D-erythro-sphingosine; N-octanoyl-D-erythro-sphingosine; N-stearoyl-D-erythro-sphingosine (C17 base); ethylenediamine core-poly (amidoamine) generation 0 dendrimer; G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]); N-octanoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)2000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)2000]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)5000]}; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane; 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine; 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; 1,2-distearoyl-sn-glycero-3-ethylphosphocholine; 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine; 1,2-di-O-tetradecyl-sn-glycero-3-phospho-(1′-rac-glycerol); and 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1′-sn-glycerol). 
     
     
         55 . The particle of  claim 53 , wherein the second amphiphile comprises one or more PEG-phospholipids. 
     
     
         56 . The particle of  claim 55 , wherein the second amphiphile comprises 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]. 
     
     
         57 . The particle of  claim 55 , wherein the second amphiphile comprises 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]. 
     
     
         58 . The particle of  claim 53 , wherein the second amphiphile comprises one or more PEG-ceramides. 
     
     
         59 . The particle of  claim 58 , wherein the second amphiphile comprises N-palmitoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}. 
     
     
         60 . The particle of any one of  claims 53 - 59 , wherein the second amphiphile is in the range from about 1% to about 50% by weight compared with the weight of the core. 
     
     
         61 . The particle of any one of  claims 53 - 60 , wherein the second amphiphile is about 10% by weight compared with the weight of the core. 
     
     
         62 . A composition comprising a particle of any one of  claims 1 - 61 , and a pharmaceutically acceptable carrier. 
     
     
         63 . The composition of  claim 62 , wherein the composition provides for sustained release of the payload. 
     
     
         64 . The composition of  claim 62 , wherein the composition provides a pharmacokinetic half-life of the payload in the range of from about 100% to about 100,000% of the half-life of a naked payload. 
     
     
         65 . The composition of  claim 62 , wherein the composition provides an AUC of the payload in the range of from about 100% to about 100,000% of the AUC of a naked payload. 
     
     
         66 . The composition of  claim 62 , wherein the composition provides a pharmacokinetic clearance of the biomolecule in the range of from about 1% to about 100% of the clearance of a naked payload. 
     
     
         67 . A method of preparing a particle according to  claim 1  comprising:
 obtaining a first solution comprising a water-insoluble polymer, a payload and a first amphiphile in a water-miscible solvent; 
 mixing the first solution with an aqueous second solution to form an aqueous composition comprising a particle according to  claim 1 . 
 
     
     
         68 . The method of  claim 67 , further comprising mixing the aqueous composition with a solution comprising a second amphiphile to form a shell surrounding the core. 
     
     
         69 . The method of  claim 67  or  68 , wherein the payload and the first amphiphile have complementary electrical charges. 
     
     
         70 . The method of any one of  claims 67 - 69 , wherein the water-insoluble polymer comprises one or more polymers selected from polyethylene glycol, poly(ethylene glycol)-co-poly(D,L-lactic acid), poly(ethylene glycol)-co-(poly(lactide-co-glycolide)), polystyrene-b-polyethylene oxide, polybutylacrylate-b-polyacrylic acid, polybutylmethacrylate-b-polyethyleneoxidepolyethylene oxide, polyethyleneimine, diethyleneglycol, triethyleneglycol, polyalkylene glycol, polyalkyline oxide, polyvinyl alcoholpolyvinylpyrrolidone, polyvinylmethylether, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyl-oxazoline, polyhydroxypropylmethacrylamide, polymethacrylamide, polydimethylacryl-amide, polyhydroxypropylmethacrylate, polyhydroxyethylacrylate, hydroxymethylcellulose, hydroxyethylcellulose, polyglycerine, polyaspartamide, polyoxyethlene-polyoxypropylene copolymer (poloxamer), poly(acrylic acid), poly(methacrylic acid), poly(itaconic acid), poly(maleic acid), polyoxyethylenes, polyethyleneoxide, polylactic acid, polypropylene oxide, poly(lactide-co-glycolide), poly(epsilon-caprolactone), poly(ethylethylene), polybutadiene, polyglycolide, polymethylacrylate, polyvinylbutylether, polystyrene, polycyclopentadienylmethylnorbornene, polyethylenepropylene, polyethylethylene, polyisobutylene, polysiloxane, poly(methyl acrylate), poly(ethyl acrylate), poly(propyl acrylate), poly(n-butyl acrylate), poly(isobutyl acrylate), poly(2-ethyl acrylate), poly(t-butyl acrylate), poly(ethyl methacrylate), poly(n-butyl methacrylate), poly(isobutyl methacrylate), poly(acrylonitriles), poly(methacrylonitrile), poly(vinyl acetate), poly(vinylversatate), poly(vinylpropionate), poly(vinylformamide), poly(vinylacetamide), poly(vinylpyridines), poly(vinyllimidazole), poly(aminoalkylacrylates), poly(aminoalkylsmethacrylates), poly(aminoalkyl(meth)acrylamides), fluorescent polymers, and polystyrenes. 
     
     
         71 . The method of any one of  claims 67 - 70 , wherein water-insoluble polymer comprises one or more polymers selected from poly(glycolic acid); poly(lactic acid); poly(caprolactone); poly(lactide-co-glycolide); poly(ortho ester) II; poly(alkyl cyanoacrylate); desaminotyrosyl octyl ester; polyphosphoesters; polyester amides; polyurethanes; chitosan; acrylates copolymer; acrylic acid-isooctyl acrylate copolymer; ammonio methacrylate copolymer; ammonio methacrylate copolymer type A; ammonio methacrylate copolymer type B; butyl ester of vinyl methyl ether/maleic anhydride copolymer (125,000 molecular weight); carbomer homopolymer type A (allyl pentaerythritol crosslinked); carbomer homopolymer type B (allyl sucrose crosslinked); cellulosic polymers; dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymer; dimethylsiloxane/methylvinylsiloxane copolymer; divinylbenzene styrene copolymer; ethyl acrylate-methacrylic acid copolymer; ethyl acrylate and methyl methacrylate copolymer (2:1; 750,000 molecular weight); ethylene vinyl acetate copolymer; ethylene-propylene copolymer; ethylene-vinyl acetate copolymer (28% vinyl acetate); glycerin polymer solution i-137; glycerin polymer solution im-137; hydrogel polymer; ink/polyethylene terephthalate/aluminum/polyethylene/sodium polymethacrylate/ethylene vinyl acetate copolymer; isooctyl acrylate/acrylamide/vinyl acetate copolymer; Kollidon® VA 64 polymer; methacrylic acid-ethyl acrylate copolymer (1:1) type A; methacrylic acid-methyl methacrylate copolymer (1:1); methacrylic acid-methyl methacrylate copolymer (1:2); methacrylic acid copolymer; methacrylic acid copolymer type A; methacrylic acid copolymer type B; methacrylic acid copolymer type C; octadecene-1/maleic acid copolymer; PEG-22 methyl ether/dodecyl glycol copolymer; PEG-45/dodecyl glycol copolymer; Polyester polyamine copolymer; poly(ethylene glycol) 1,000; poly(ethylene glycol) 1,450; poly(ethylene glycol) 1,500; poly(ethylene glycol) 1,540; poly(ethylene glycol) 200; poly(ethylene glycol) 20,000; poly(ethylene glycol) 200,000; poly(ethylene glycol) 2,000,000; poly(ethylene glycol) 300; poly(ethylene glycol) 300-1,600; poly(ethylene glycol) 300-1,600; poly(ethylene glycol) 3,350; poly(ethylene glycol) 3,500; poly(ethylene glycol) 400; poly(ethylene glycol) 4,000; poly(ethylene glycol) 4,500; poly(ethylene glycol) 540; poly(ethylene glycol) 600; poly(ethylene glycol) 6,000; poly(ethylene glycol) 7,000; poly(ethylene glycol) 7,000,000; poly(ethylene glycol) 800; poly(ethylene glycol) 8,000; poly(ethylene glycol) 900; polyvinyl chloride-polyvinyl acetate copolymer; povidone acrylate copolymer; povidone/eicosene copolymer; polyoxy(methyl-1,2-ethanediyl), alpha-hydro-omega-hydroxy-, polymer with 1,1′-methylenebis[4-isocyanatocyclohexane] copolymer; polyvinyl methyl ether/maleic acid copolymer; styrene/isoprene/styrene block copolymer; vinyl acetate-crotonic acid copolymer; {poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)]}, and {poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]}. 
     
     
         72 . The method of  claim 71 , wherein the water-insoluble polymeric core comprises {poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)]}. 
     
     
         73 . The method of  claim 71 , wherein the water-insoluble polymeric core comprises {poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]}. 
     
     
         74 . The method of any one of  claims 67 - 71 , wherein the water-insoluble polymer comprises one or more polymers selected from polylactic acids, polyglycolic acids, and copolymers of lactic acid and glycolic acid. 
     
     
         75 . The method of  claim 74 , wherein the water-insoluble polymer comprises one or more copolymers of lactic acid and glycolic acid. 
     
     
         76 . The method of  claim 75 , wherein the water-insoluble polymer comprises a copolymer of lactic acid and glycolic acid that comprises lactic acid and glycolic acid monomer units in a ratio of about 1:1. 
     
     
         77 . The method of any one of  claims 67 - 76 , wherein the first amphiphile is cationic. 
     
     
         78 . The method of any one of  claims 67 - 76 , wherein the first amphiphile is anionic. 
     
     
         79 . The method of any one of  claims 65 - 76 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: lecithin, amino dendrimers, PEG-phospholipids, PEG-ceramides, anionic lipids, and cationic lipids. 
     
     
         80 . The method of  claim 79 , wherein the first amphiphile comprises an amino dendrimer. 
     
     
         81 . The method of  claim 79 , wherein the first amphiphile comprises a cationic lipid. 
     
     
         82 . The method of any one of  claims 67 - 76 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: lecithin; G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]); N-octanoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)2000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)2000]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)5000]}; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane; 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine; 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; 1,2-distearoyl-sn-glycero-3-ethylphosphocholine; 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine; 1,2-di-O-tetradecyl-sn-glycero-3-phospho-(1′-rac-glycerol); and 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1′-sn-glycerol). 
     
     
         83 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises one or more compounds selected from the group consisting of: G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane. 
     
     
         84 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises G0-C14 dendrimer. 
     
     
         85 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises polypropylenimine tetramine dendrimer, generation 1. 
     
     
         86 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises ethylenediamine branched polyethylenimine. 
     
     
         87 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises 1,2-dioleoyl-3-trimethylammonium-propane. 
     
     
         88 . The method of any one of  claims 67 - 77 , wherein the first amphiphile comprises 1,2-di-O-octadecenyl-3-trimethylammonium propane. 
     
     
         89 . The method of any one of  claims 67 - 77 , wherein the water-insoluble core comprises the first amphiphile in an amount from about 1% to about 50% by weight. 
     
     
         90 . The method of  claim 89 , wherein the water-insoluble core comprises the first amphiphile in an amount from about 10% to about 20% by weight. 
     
     
         91 . The method of any one of  claims 67 - 90 , wherein the payload comprises a small molecule. 
     
     
         92 . The method of any one of  claims 67 - 90 , wherein the payload comprises a biomolecule. 
     
     
         93 . The method of any one of  claims 67 - 92 , wherein the payload is anionic. 
     
     
         94 . The method of any one of  claims 67 - 92 , wherein the payload is cationic. 
     
     
         95 . The method of any one of  claims 67 - 94 , wherein the payload comprises one or more species selected from the group consisting of: polypeptides; proteins; nucleic acids; polypeptide hormones; antibody-drug conjugates; antibody fragment-drug conjugates; protein-drug conjugates; peptide-drug conjugates; fusion proteins; enzymes; monoclonal antibodies; bispecific monoclonal antibodies; and multimeric fusion proteins. 
     
     
         96 . The method of  claim 95 , wherein the payload comprises a protein. 
     
     
         97 . The method of  claim 96 , wherein the payload is enhanced green fluorescent protein. 
     
     
         98 . The method of any one of  claims 67 - 94 , wherein the payload comprises one or more species selected from the group consisting of: transforming growth factor-beta, interferons, colony stimulating factors, granulocyte colony stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17, interleukin-18, interleukin-22, interleukin-23, interleukin-35, atacicept, abatacept, alefacept, etanercept, romiplostim, rilonacept, adalimumab, alemtuzumab, atlizumab, canakinumab, certolizumab, certolizumab pegol, daclizumab, efalizumab, fontolizumab, golimumab, infliximab, mepolizumab, natalizumab, omalizumab, ruplizumab, ustekinumab, visilizumab, zanolimumab, vedolizumab, belimumab, otelixizumab, teplizumab, rituximab, ofatumumab, ocrelizumab, epratuzumab, eculizumab, and briakinumab. 
     
     
         99 . The method of any one of  claims 67 - 94 , wherein the payload comprises one or more species selected from the group consisting of: abagovomab, adecatumumab, afutuzumab, alacizumab pegol, altumomab pentetate, amatuximab, anatumomab mafenatox, apolizumab, arcitumomab, bavituximab, bectumomab, belimumab, bevacizumab, bivatuzumab mertansine, blinatumomab, brentuximab vedotin, cantuzumab mertansine, cantuzumab ravtansine, capromab pendetide, cetuximab, citatuzumab bogatox, cixutumumab, clivatuzumab tetraxetan, dacetuzumab, demcizumab, detumomab, drozitumab, ecromeximab, eculizumab, elotuzumab, ensituximab, epratuzumab, etaracizumab, farletuzumab, figitumumab, flanvotumab, galiximab, gemtuzumab ozogamicin, girentuximab, ibritumomab tiuxetan, imgatuzumab, ipilimumab, labetuzumab, lexatumumab, lorvotuzumab mertansine, nimotuzumab, ofatumumab, oregovomab, panitumumab, pemtumomab, pertuzumab, tacatuzumab tetraxetan, tositumomab, trastuzumab, totumumab, and zalutumumab. 
     
     
         100 . The method of any one of  claims 67 - 94 , wherein the payload comprises one or more species selected from the group consisting of: agalsidase beta, imiglucerase, velaglucerase alfa, taliglucerase, alglucosidase alfa, laronidase, idursulfase, and galsulfase. 
     
     
         101 . The method of any one of  claims 67 - 94 , wherein the payload comprises a nucleic acid. 
     
     
         102 . The method of  claim 101 , wherein the nucleic acid is double stranded. 
     
     
         103 . The method of  claim 101 , wherein the nucleic acid is single stranded. 
     
     
         104 . The method of any one of  claims 101 - 103 , wherein the nucleic acid comprises a vector. 
     
     
         105 . The method of  claim 104 , wherein the vector is selected from a plasmid and a viral vector. 
     
     
         106 . The method of  claim 105 , wherein the viral vector comprises one or more vectors selected from the group consisting of retroviral vectors, lentiviral vectors, adenoviral vectors, and adeno-associated viral vectors. 
     
     
         107 . The method of  claim 101 , wherein the nucleic acid is a DNA. 
     
     
         108 . The method of  claim 101 , wherein the nucleic acid is an RNA. 
     
     
         109 . The method of  claim 108 , wherein the nucleic acid is selected from the group consisting of siRNAs, microRNAs, and mRNAs. 
     
     
         110 . The method of  claim 109 , wherein the nucleic acid is siRNA. 
     
     
         111 . The method of  claim 110 , wherein siRNA is selected from the group consisting of siPHB1, siMYC, si-c-MYC, siBRAF, and siBRAF V600E . 
     
     
         112 . The method of  claim 109 , wherein the nucleic acid is microRNA. 
     
     
         113 . The method of  claim 109 , wherein the nucleic acid is mRNA. 
     
     
         114 . The method of  claim 101 , wherein the nucleic acid decreases expression of a protein selected from kinesin spindle protein, RRM2, keratin 6a, HER1, ErbB2, VEGFR1, VEGFR3), PDGFR-α, PDGFR-β, EGFR, FGFR1, FGFR2, FGFR3, FGFR4, EphA2, EphA3, EphA4, HER2, HER3, HER4, INS-R, IGF-1R, IR-R, CSF1R, KIT, FLK-II, KDR/FLK-1, FLK-4, flt-1, c-Met, Ron, Sea, TRKA, TRKB, TRKC, FLT3, VEGFR/Flt2, Flt4, EphA1, EphB2, EphB4, Pim1, Pim2, Pim3, Tie2PKN3, PLK1, PLK2, PLK3, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, Abl, Kit, KDR, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAP kinase, PI3K, Akt1, Akt2, Akt3, TGF-βR, KRAS, BRAF, CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK9, GSK3, CLK1, CLK4, Aurora A, Aurora B, Aurora C, MEK1, MEK2, mTOR, protein kinase A, protein kinase C, protein kinase G, and PHB1. 
     
     
         115 . The method of  claim 101 , wherein the nucleic acid decreases expression of a protein selected from kinesin spindle protein, RRM2, keratin 6a, HER1, ErbB2, VEGFR1, VEGFR3), PDGFR-α, PDGFR-β, EGFR, FGFR1, FGFR2, FGFR3, FGFR4, EphA2, EphA3, EphA4, HER2, HER3, HER4, INS-R, IGF-1R, IR-R, CSF1R, KIT, FLK-II, KDR/FLK-1, FLK-4, flt-1, c-Met, Ron, Sea, TRKA, TRKB, TRKC, FLT3, VEGFR/Flt2, Flt4, EphA1, EphB2, EphB4, Pim1, Pim2, Pim3, Tie2PKN3, PLK1, PLK2, PLK3, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, Abl, Kit, KDR, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAP kinase, PI3K, Akt1, Akt2, Akt3, TGF-βR, KRAS, BRAF, BRAF V600E , CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK9, GSK3, CLK1, CLK4, Aurora A, Aurora B, Aurora C, MEK1, MEK2, mTOR, protein kinase A, protein kinase C, protein kinase G, MYC, c-MYC and PHB1. 
     
     
         116 . The method of  claim 101 , wherein the nucleic acid decreases expression of a viral region selected from the group consisting of: L segments, M segments, and S segments. 
     
     
         117 . The method of any one of  claims 67 - 115 , wherein the second amphiphile comprises one or more compounds selected from neutral lipids, amino dendrimers, PEG-phospholipids, PEG-ceramides, anionic lipids, and cationic lipids. 
     
     
         118 . The method of  claim 117 , wherein the second amphiphile comprises one or more selected from the group consisting of: lecithin; 1,2-dioctanoyl-sn-glycerol; 1,2-didecanoyl-sn-glycerol; D-erythro-sphingosine; D-glucosyl-β-1,1′ N-octanoyl-D-erythro-sphingosine; N-butyroyl-D-erythro-sphingosine; N-octanoyl-D-erythro-sphingosine; N-stearoyl-D-erythro-sphingosine (C17 base); ethylenediamine core-poly (amidoamine) generation 0 dendrimer; G0-C14 dendrimer; ethylenediamine branched polyethylenimine; polypropylenimine tetramine dendrimer, generation 1; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-350]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-550]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-1000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]; 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]; 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]); N-octanoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)750]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)2000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)2000]}; N-octanoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}; N-palmitoyl-sphingosine-1-{succinyl[methoxy(polyethylene glycol)5000]}; 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol; 1,2-dioleoyl-3-trimethylammonium-propane; 1-oleoyl-2-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-3-trimethylammonium propane; 1,2-dimyristoyl-3-trimethylammonium-propane; 1,2-dipalmitoyl-3-trimethylammonium-propane, 1,2-stearoyl-3-trimethylammonium-propane; 1,2-di-O-octadecenyl-3-trimethylammonium propane; 1,2-dilauroyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; 1,2-dimyristoleoyl-sn-glycero-3-ethylphosphocholine; 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine; 1,2-distearoyl-sn-glycero-3-ethylphosphocholine; 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine; 1,2-di-O-tetradecyl-sn-glycero-3-phospho-(1′-rac-glycerol); and 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1′-sn-glycerol). 
     
     
         119 . The method of  claim 117 , wherein the second amphiphile comprises one or more PEG-phospholipids. 
     
     
         120 . The method of  claim 119 , wherein the second amphiphile comprises 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-3000]. 
     
     
         121 . The method of  claim 119 , wherein the second amphiphile comprises 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]. 
     
     
         122 . The method of  claim 117 , wherein the second amphiphile comprises one or more PEG-ceramides. 
     
     
         123 . The method of  claim 122 , wherein the second amphiphile comprises N-palmitoyl-sphingosine-1-{succinyl [methoxy(polyethylene glycol)5000]}. 
     
     
         124 . The method of any one of  claims 117 - 123 , wherein the second amphiphile is in the range from about 1% to about 50% by weight compared with the weight of the core. 
     
     
         125 . The method of any one of  claims 117 - 124 , wherein the second amphiphile is about 10% by weight compared with the weight of the core. 
     
     
         126 . A method of administering a therapeutic payload to a subject in need thereof, comprising administering to the subject one or more particles of any one of  claims 1 - 61 , or composition of any one of  claims 62 - 66 , wherein the one or more particles is administered in an amount that provides to the subject a therapeutically effective amount of the payload. 
     
     
         127 . A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a particle of any one of  claims 1 - 61  or a composition of any one of  claims 62 - 66 , wherein the payload is indicated for treatment of the cancer. 
     
     
         128 . A method of treating a disease or a condition in need of enzyme replacement in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a particle of any one of  claims 1 - 61 , or a composition of any one of  claims 62 - 66 , wherein the payload is indicated for treating the disease or condition in need of enzyme replacement. 
     
     
         129 . A method of preventing or treating a viral disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a particle of any one of  claims 1 - 61 , or a composition of any one of  claims 62 - 66 , wherein the payload is indicated for treatment of the viral disease. 
     
     
         130 . A method of treating an inflammatory disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a particle of any one of  claims 1 - 61 , or a composition of any one of  claims 62 - 66 , wherein the payload is indicated for treatment of the inflammatory disease. 
     
     
         131 . The method of  claim 130 , wherein the inflammatory disease or condition is selected from the group consisting of: atherosclerosis, Alzheimer's disease, arthritis, multiple sclerosis, rheumatoid arthritis, psoriasis, psoriatic arthritis, osteoarthritis, degenerative arthritis, polymyalgia rheumatic, ankylosing spondylitis, reactive arthritis, gout, pseudogout, inflammatory joint disease, systemic lupus erythematosus, polymyositis, fibromyalgia, achilles tendinitis, achondroplasia, acromegalic arthropathy, adhesive capsulitis, adult onset Still's disease, anserine bursitis, avascular necrosis, Behcet's syndrome, bicipital tendinitis, Blount's disease, brucellar spondylitis, bursitis, calcaneal bursitis, calcium pyrophosphate dihydrate deposition disease (CPPD), crystal deposition disease, Caplan's syndrome, carpal tunnel syndrome, chondrocalcinosis, chondromalacia patellae, chronic synovitis, chronic recurrent multifocal osteomyelitis, Churg-Strauss syndrome, Cogan's syndrome, corticosteroid-induced osteoporosis, costosternal syndrome, CREST syndrome, cryoglobulinemia, degenerative joint disease, dermatomyositis, diabetic finger sclerosis, diffuse idiopathic skeletal hyperostosis (DISH), discitis, discoid lupus erythematosus, drug-induced lupus, Duchenne's muscular dystrophy, Dupuytren's contracture, Ehlers-Danlos syndrome, enteropathic arthritis, epicondylitis, erosive inflammatory osteoarthritis, exercise-induced compartment syndrome, Fabry's disease, familial Mediterranean fever, Farber's lipogranulomatosis, Felty's syndrome, Fifth's disease, flat feet, foreign body synovitis, Freiberg's disease, fungal arthritis, Gaucher's disease, giant cell arteritis, gonococcal arthritis, Goodpasture's syndrome, granulomatous arteritis, hemarthrosis, hemochromatosis, Henoch-Schonlein purpura, Hepatitis B surface antigen disease, hip dysplasia, Hurler syndrome, hypermobility syndrome, hypersensitivity vasculitis, hypertrophic osteoarthropathy, immune complex disease, impingement syndrome, Jaccoud's arthropathy, juvenile ankylosing spondylitis, juvenile dermatomyositis, juvenile rheumatoid arthritis, Kawasaki disease, Kienbock's disease, Legg-Calve-Perthes disease, Lesch-Nyhan syndrome, linear scleroderma, lipoid dermatoarthritis, Lofgren's syndrome, Lyme disease, malignant synovioma, Marfan's syndrome, medial plica syndrome, metastatic carcinomatous arthritis, mixed connective tissue disease (MCTD), mixed cryoglobulinemia, mucopolysaccharidosis, multicentric reticulohistiocytosis, multiple epiphyseal dysplasia, mycoplasmal arthritis, myofascial pain syndrome, neonatal lupus, neuropathic arthropathy, nodular panniculitis, ochronosis, olecranon bursitis, Osgood-Schlatter's disease, osteoarthritis, osteochondromatosis, osteogenesis imperfecta, osteomalacia, osteomyelitis, osteonecrosis, osteoporosis, overlap syndrome, pachydermoperiostosis, Paget's disease of bone, palindromic rheumatism, patellofemoral pain syndrome, Pellegrini-Stieda syndrome, pigmented villonodular synovitis, piriformis syndrome, plantar fasciitis, polyarteritis nodos, polymyalgia rheumatica, polymyositis, popliteal cysts, posterior tibial tendinitis, Potts disease, prepatellar bursitis, prosthetic joint infection, pseudoxanthoma elasticum, psoriatic arthritis, Raynaud's phenomenon, reactive arthritis/Reiter's syndrome, reflex sympathetic dystrophy syndrome, relapsing polychondritis, reperfusion injury, retrocalcaneal bursitis, rheumatic fever, rheumatoid vasculitis, rotator cuff tendinitis, sacroiliitis, salmonella osteomyelitis, sarcoidosis, saturnine gout, Scheuermann's osteochondritis, scleroderma, septic arthritis, seronegative arthritis, shigella arthritis, shoulder-hand syndrome, sickle cell arthropathy, Sjogren's syndrome, slipped capital femoral epiphysis, spinal stenosis, spondylolysis, staphylococcus arthritis, Stickler syndrome, subacute cutaneous lupus, Sweet's syndrome, Sydenham's chorea, syphilitic arthritis, systemic lupus erythematosus (SLE), Takayasu's arteritis, tarsal tunnel syndrome, tennis elbow, Tietse's syndrome, transient osteoporosis, traumatic arthritis, trochanteric bursitis, tuberculosis arthritis, arthritis of Ulcerative colitis, undifferentiated connective tissue syndrome (UCTS), urticarial vasculitis, viral arthritis, Wegener's granulomatosis, Whipple's disease, Wilson's disease, and yersinial arthritis.