PEPTIDE PARTICLES AND METHODS OF FORMATION
The present disclosure relates to compositions and methods that enable the formation of pharmaceutically relevant particles that can be used for therapy. In particular, the methods disclosed herein allow the controlled formation of circular particles comprising biologically active peptides.
1 . A particle comprising a peptide, wherein the particle comprises up to about 10% (w/w) of peptide and the circularity of the particle is from about 0.80 to about 1.00.
2 . The particle of claim 1 , wherein the peptide is a biologically active peptide.
3 . The particle of claim 2 , wherein the biologically active peptide comprises from about 2 to about 12 amino acid residues.
4 .- 17 . (canceled)
18 . The particle of claim 1 , wherein the particle has a diameter of about 5 to about 50 μm.
19 .- 28 . (canceled)
29 . The particle of claim 1 , further comprising a carbohydrate, a protein stabilizer, an emulsifier, an amino acid, a surfactant, or a combination thereof.
30 . The particle of claim 29 , wherein the carbohydrate is dextran, trehalose, sucrose, agarose, mannitol, lactose, sorbitol, maltose, or a combination thereof.
31 . The particle of claim 29 , wherein the protein stabilizer is trehalose, polyethylene glycol (PEG), polyoxamers, polyvinylpyrrolidone, polyacrylic acids, poly(vinyl) polymers, polyesters, polyaldehydes, tert-polymers, polyamino acids, hydroxyethylstarch, N-methyl-2-pyrrolidone, sorbitol, sucrose, mannitol, cyclodextrin, hydroxypropyl beta-cyclodextrin, sulfobutylether beta-cyclodextrin, or a combination thereof.
32 . The particle of claim 29 , wherein the emulsifier is polysorbate, sorbitan monooleate, ethanolamine, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, carbomer 1342, a corn oil-mono-di-triglyceride, a polyoxyethylated oleic glyceride, a poloxamer, or a combination thereof.
33 . The particle of claim 29 , wherein the amino acid is alanine, aspartic acid, cysteine, isoleucine, glutamic acid, leucine, methionine, phenylalanine, pyrrolysine, serine, selenocysteine, threonine, tryptophan, tyrosine, valine, asparagine, arginine, histidine, glycine, glutamine, proline, or a combination thereof.
34 . The particle of claim 29 , wherein the surfactant is polysorbate, magnesium stearate, sodium dodecyl sulfate, TRITON™ N-101, glycerin, polyoxyethylated castor oil, docusate, sodium stearate, decyl glucoside, nonoxynol-9, cetyltrimethylammonium bromide, sodium bis(2-ethylhexyl) sulfosuccinate, lecithin, sorbitan ester, or a combination thereof.
35 . The particle of claim 1 , wherein the particle has a surfactant content of less than about 10% by mass.
36 . The particle of claim 35 , wherein the particle has a surfactant content of less than about 5% by mass.
37 . The particle of claim 36 , wherein the particle has a surfactant content of less than about 3% by mass.
38 . The particle of claim 37 , wherein the particle has a surfactant content of less than about 1% by mass.
39 . The particle of claim 38 , wherein the particle has a surfactant content of less than about 0.1% by mass.
40 .- 41 . (canceled)
42 . The particle of claim 1 , wherein the particle has less than about 5% residual moisture by weight.
43 . The particle of claim 42 , wherein the particle has less than about 3% residual moisture by weight.
44 . The particle of claim 43 , wherein the particle has less than about 1% residual moisture by weight.
45 . A composition comprising a plurality of particles, each particle comprising a peptide suspended in a liquid, wherein the particles comprise up to about 10% (w/w) of peptide and the circularity of the particles is from about 0.80 to about 1.00.
46 .- 123 . (canceled)
124 . A method of forming particles, the method comprising:
a) providing droplets comprising a first liquid and a peptide;
b) contacting the droplets comprising the peptide with a second liquid;
c) allowing the droplets to dry; and
d) removing the first and second liquids,
thereby forming particles comprising a peptide, wherein the particles comprise up to about 10% (w/w) of peptide and the circularity of the particles is from about 0.80 to about 1.00 after removing the first and second liquids.
125 .- 219 . (canceled)