Peptide nanoparticles and uses therefor

Abstract

The present invention provides nanoparticle compositions including one or more peptides. The present invention achieves transdermal delivery of such peptides without the need for peptide modification, or for use of chemical or mechanical abrasion or disruption of skin.

1 . An oil-in-water or water-in-oil dispersion of comprising a population of particles,
 wherein the majority of particles have diameters between approximately 10 and approximately 300 nanometers;   wherein the particles have an average particle size ranging between 50 nanometers and about 250 nanometers; and   wherein said particles comprise at least one unmodified peptide of length between 2 and 30 amino acids that has biological activity in the skin, subcutaneous tissue or contiguous muscles; and   wherein the at least one unmodified peptide promotes extra-cellular matrix production, decreases wrinkles, improves wound healing, or treats excessive accumulation of extra-cellular matrix.   
     
     
         2 .- 80 . (canceled) 
     
     
         81 . The dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 250 nanometers, or between approximately 10 and approximately 200 nanometers, or between approximately 10 and approximately 150 nanometers, or between approximately 10 and approximately 120 nanometers, or between approximately 10 and approximately 100 nanometers, or between approximately 10 and approximately 50 nanometers. 
     
     
         82 . The dispersion of  claim 1 , wherein the dispersion is a nanoemulsion. 
     
     
         83 . The dispersion of  claim 82 , wherein the nanoemulsion comprises at least one oil, at least one surfactant, water, and the unmodified peptide. 
     
     
         84 . The dispersion of  claim 1 , further comprising an oil. 
     
     
         85 . The dispersion of  claim 84 , wherein the oil is selected from the group consisting of almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, jojoba, kukui nut, lavandin, lavender, lemon,  Litsea cubeba , macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, soy sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils; butyl stearate; caprylic triglyceride; capric triglyceride; cyclomethicone; diethyl sebacate; dimethicone 360; isopropyl myristate; mineral oil; octyldodecanol; oleyl alcohol; silicone oil; short chain triglycerides; medium chain triglycerides; Labrafac WL 1349; long chain triglycerides; saturated oils thereof; and unsaturated oils thereof. 
     
     
         86 . The dispersion of  claim 85 , wherein the oil is soybean. 
     
     
         87 . The dispersion of  claim 85 , wherein the oil is a medium chain triglyceride. 
     
     
         88 . The dispersion of  claim 1 , further comprising a surfactant. 
     
     
         89 . The dispersion of  claim 88 , wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleylphosphatidyl ethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleoyl-phosphatidylcholine; cholesterol; cholesterol ester; diacylglycerol; diacylglycerolsuccinate; diphosphatidyl glycerol (DPPG); hexanedecanol; fatty alcohols such as polyethylene glycol (PEG); polyoxyethylene-9-lauryl ether; a surface active fatty acid, such as palmitic acid or oleic acid; fatty acids; fatty acid monoglycerides; fatty acid diglycerides; fatty acid amides; sorbitan trioleate (Span 85) glycocholate; sorbitan monolaurate (Span 20); polysorbate 20 (Tween-20); polysorbate 60 (Tween-60); polysorbate 65 (Tween-65); polysorbate 80 (Tween-80); polysorbate 85 (Tween-85); polyoxyethylene monostearate; surfactin; a poloxomer; a sorbitan fatty acid ester such as sorbitan trioleate; lecithin; lysolecithin; phosphatidylserine; phosphatidylinositol; sphingomyelin; phosphatidylethanolamine (cephalin); cardiolipin; phosphatidic acid; cerebrosides; dicetylphosphate; dipalmitoylphosphatidylglycerol; stearylamine; dodecylamine; hexadecyl-amine; acetyl palmitate; glycerol ricinoleate; hexadecyl sterate; isopropyl myristate; tyloxapol; poly(ethylene glycol)5000-phosphatidylethanolamine; poly(ethylene glycol)400-mono-stearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; and ion pairing agents. 
     
     
         90 . The dispersion of  claim 89 , wherein the surfactant is a polysorbate. 
     
     
         91 . The dispersion of  claim 1 , further comprising an oil and a surfactant. 
     
     
         92 . The dispersion of  claim 91 , wherein the ratio of surfactant to oil is approximately 0.25:1 by weight; approximately 0.5:1 by weight; approximately 1:1 by weight; approximately 2:1 by weight; or approximately 3:1 by weight. 
     
     
         93 . The dispersion of  claim 1 , wherein the at least one unmodified peptide treats hypertrophic scarring, keloids, localized sclerosis, systemic sclerosis, or other condition characterized by excess accumulation of the extra-cellular matrix. 
     
     
         94 . The dispersion of  claim 1 , wherein the at least one unmodified peptide has a cosmetic effect on the skin. 
     
     
         95 . A method, comprising steps of:
 administering an amount of an oil-in-water or water-in-oil dispersion to skin of a subject,   wherein the dispersion comprises a population of particles, wherein the majority of particles have diameters between approximately 10 and approximately 300 nanometers, and wherein the particles have an average particle size ranging between 50 nanometers and about 250 nanometers;   wherein the particles comprises at least one unmodified peptide of length between 2 and 30 amino acids that has biological activity in the skin, subcutaneous tissue or contiguous muscles, and   wherein the at least one modified peptide promotes extra-cellular matrix production, decreases wrinkles, improves wound healing, or treats excessive accumulation of extra-cellular matrix.   
     
     
         96 . The method of  claim 95 , wherein the subject has at least one symptom of facial wrinkles, and
 wherein the dispersion is administered to skin of the subject in an amount effective to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, or reduce incidence of, facial wrinkles.   
     
     
         97 . The method of  claim 95 , wherein the subject has at least one symptom of hypertrophic scarring, keloids, localized sclerosis, systemic sclerosis, or other condition characterized by excess accumulation of the extracellular matrix; and
 wherein the dispersion is administered to skin of the subject at an amount effective to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, or reduce incidence of the at least one symptom associated with hypertrophic scarring, keloids, localized sclerosis, systemic sclerosis, or other condition characterized by excess accumulation of the extracellular matrix.   
     
     
         98 . The method of  claim 95 , wherein at least 50% of the unmodified peptide permeates the skin of the subject. 
     
     
         99 . A method of manufacturing the dispersion of  claim 1 , the method comprising:
 providing a premix comprising an oil, a surfactant, water, and the at least one unmodified peptide;   subjecting the premix to high shear force or high pressure homogenization for a period of time and under conditions which achieve the dispersion of  claim 1 .