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 . A suspension or dispersion of nanoparticles comprising a population of particles, wherein the majority of particles have diameters between approximately 10 and approximately 300 nanometers, and wherein said nanoparticles 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. 
     
     
         2 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 250 nanometers. 
     
     
         3 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 200 nanometers. 
     
     
         4 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 150 nanometers. 
     
     
         5 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 120 nanometers. 
     
     
         6 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 100 nanometers. 
     
     
         7 . The suspension or dispersion of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 50 nanometers. 
     
     
         8 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises KTTKS. 
     
     
         9 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises EYKTTKSSRL. 
     
     
         10 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises VIEYKTTK. 
     
     
         11 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises KTTK. 
     
     
         12 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises GKTVIEYKTTKS. 
     
     
         13 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises GKTVIEYKTTKSSRL. 
     
     
         14 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises WGKTVIEYKTTKSSRLPIID. 
     
     
         15 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises CTSHTGAWGKTVIEYKTTKS. 
     
     
         16 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises TTKS. 
     
     
         17 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises EEMQRR. 
     
     
         18 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises gastrin-releasing peptide. 
     
     
         19 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises VGVAPG. 
     
     
         20 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises YYRADA. 
     
     
         21 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises GHK. 
     
     
         22 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises TTKS. 
     
     
         23 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises interferon. 
     
     
         24 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises interferon inducer. 
     
     
         25 . The suspension or dispersion of  claim 1 , wherein said nanoparticles comprise an unmodified peptide whose amino acid sequence comprises P144. 
     
     
         26 . The suspension or dispersion of  claim 1 , wherein the nanoparticle is a nanoemulsion. 
     
     
         27 . The suspension or dispersion of  claim 26 , wherein the nanoemulsion comprises at least one oil, at least one surfactant, water, and the unmodified peptide. 
     
     
         28 . The suspension or dispersion of  claim 26 , wherein the nanoemulsion comprises a single oil, a single surfactant, water, and the unmodified peptide. 
     
     
         29 . (canceled) 
     
     
         30 . The suspension or dispersion of  claim 1 , further comprising an oil, and 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, 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. 
     
     
         31 . The suspension or dispersion of  claim 30 , wherein the oil is soy oil. 
     
     
         32 . The suspension or dispersion of  claim 30 , wherein the oil is a medium chain triglyceride. 
     
     
         33 . The suspension or dispersion of  claim 30 , wherein the oil is Labrafac WL 1349. 
     
     
         34 . The suspension or dispersion of  claim 1 , further comprising a surfactant, wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleylphosphatidyl ethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleoylphosphatidylcholine; 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-monostearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; and ion pairing agents. 
     
     
         35 . The suspension or dispersion of  claim 34 , wherein the surfactant is Tween. 
     
     
         36 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil ranges between 0.5:1 and approximately 2:1 by weight. 
     
     
         37 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil is approximately 0.25:1 by weight. 
     
     
         38 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil is approximately 0:5:1 by weight. 
     
     
         39 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil is approximately 1:1 by weight. 
     
     
         40 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil is approximately 2:1 by weight. 
     
     
         41 . The suspension or dispersion of  claim 1 , further comprising an oil and a surfactant, wherein the ratio of surfactant to oil is approximately 3:1 by weight. 
     
     
         42 . The suspension or dispersion of  claim 1 , wherein the nanoparticle is a nanomicelle. 
     
     
         43 . The suspension or dispersion of  claim 1 , further comprising at least one additional component that, together with the suspension or dispersion, creates a cream, oil, ointment, gel, spray, lipstick, or sunscreen. 
     
     
         44 . A method, comprising steps of:
 providing a subject; and   administering an amount of the suspension or dispersion of  claim 1  to the subject's skin such that a cosmetic or therapeutic benefit is attained.   
     
     
         45 . The method of  claim 44 ,
 wherein the suspension or dispersion is administered to the subject's skin at an amount effective to thicken the subject's skin or subcutaneous tissue.   
     
     
         46 . The method of  claim 44 ,
 wherein the step of providing a subject comprises providing a subject suffering from, susceptible to, or exhibiting at least one symptom of fine skin lines; and   wherein the suspension or dispersion is administered to the subject's skin at an amount effective to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, or reduce incidence of the fine skin lines.   
     
     
         47 . The method of  claim 44 ,
 wherein the step of providing a subject comprises providing a subject suffering from, susceptible to, or exhibiting at least one symptom of facial wrinkles; and   wherein the suspension or dispersion is administered to the subject's skin at effective to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, or reduce incidence of facial wrinkles.   
     
     
         48 . The method of  claim 44 ,
 providing a subject; and   wherein the suspension or dispersion is administered to the subject's skin at effective to improve the appearance of the subject's skin.   
     
     
         49 . The method of  claim 44 ,
 providing a subject; and   wherein the suspension or dispersion is administered to the subject's skin at an amount effective to maintain the appearance of the subject's skin.   
     
     
         50 . The method of  claim 44 ,
 wherein the step of providing a subject comprises providing a subject suffering from a wound; and   wherein the suspension or dispersion is administered to the subject's skin at an amount effective to treat, alleviate, ameliorate, relieve, inhibit progression of, or reduce severity of the wound.   
     
     
         51 . The method of  claim 44 ,
 wherein the step of providing a subject comprises providing a subject suffering from, susceptible to, or exhibiting 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 suspension or dispersion is administered to the subject's skin 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.   
     
     
         52 . The method of any  claim 44 , wherein the step of administering is performed by hand, with a gloved finger, with an unprotected finger, by a device, with an adhesive patch, with a spatula, with a swab, with a syringe without a needle, or with a device that permits application of the suspension or dispersion to a target site on the skin without applying the suspension or dispersion to non-target sites of the skin. 
     
     
         53 - 61 . (canceled) 
     
     
         62 . The method of  claim 44 , wherein at least 99% of the unmodified peptide permeates the skin. 
     
     
         63 . The method of  claim 44 , wherein at least 95% of the unmodified peptide permeates the skin. 
     
     
         64 . The method of  claim 44 , wherein at least 90% of the unmodified peptide permeates the skin. 
     
     
         65 . The method of  claim 44 , wherein at least 75% of the unmodified peptide permeates the skin. 
     
     
         66 . The method of  claim 44 , wherein at least 50% of the unmodified peptide permeates the skin. 
     
     
         67 . The method of  claim 44 , wherein at least 25% of the unmodified peptide permeates the skin. 
     
     
         68 . The method of  claim 44 , wherein at least 10% of the unmodified peptide permeates the skin. 
     
     
         69 . The method of  claim 44 , wherein at least 1% of the unmodified peptide permeates the skin. 
     
     
         70 . A method, comprising steps of:
 providing a premix comprising an oil, a surfactant, water, and an unmodified peptide; and   subjecting the premix to high shear force or high pressure homogenization for a period of time and under conditions which achieve the suspension or dispersion of  claim 1 .   
     
     
         71 . The method of  claim 70 , wherein the step of subjecting the premix to high shear force or high pressure homogenization is achieved by microfluidization. 
     
     
         72 . The method of  claim 70 , wherein the ratio of oil and surfactant in the premix ranges between approximately 0.5:1 and approximately 2:1 by weight. 
     
     
         73 - 77 . (canceled) 
     
     
         78 . A method for identifying unmodified peptides that improve the appearance of skin, comprising steps of:
 providing:
 at least one sample of skin; and 
 at least one suspension or dispersion, wherein the suspension or dispersion comprises at least one unmodified peptide; 
   administering the suspension or dispersion to the sample of skin; and   monitoring the effect of the suspension or dispersion on the appearance of the sample of skin relative to the effect of a control substance.   
     
     
         79 - 80 . (canceled)