Lipid vesicle compositions with penetration enhancing agents

Abstract

The present application is related to a pharmaceutical composition a biphasic lipid vesicle comprising a lipid bilayer comprising vesicle forming lipids; an oil-in-water emulsion stabilized by one or more surfactants; one or more compounds; and one or more penetration enhancing agents. The one or more penetration enhancing agents include one or more non-ionic surfactants having a hydrophilic-lipophilic balance (HLB) of about 10 or less, alone or combination with one or more penetration enhancing agents selected from one or more of terpenes, alkaloids, salicylate derivatives, and polycationic surfactants and combinations thereof. The present application is also related to a pharmaceutical composition comprising a biphasic lipid vesicle comprising a lipid bilayer comprising vesicle forming lipids; an oil-in-water emulsion stabilized by one or more polycationic surfactants; and one or more compounds.

1 . A method of treating or preventing a skin condition related to excessive or defective collagen production in a subject in need thereof, the method comprising administering to the subject in need thereof, an effective amount of one or more biphasic lipid vesicles, wherein a biphasic lipid vesicle comprises a plurality of concentric lipid bilayers, and wherein the biphasic lipid vesicle comprises one or more compounds therapeutically effective in treating the skin condition related to excessive or defective collagen production. 
     
     
         2 . The method of  claim 1 , wherein the skin condition related to excessive or defective collagen is skin aging, skin elasticity, striae, stretchmarks, wrinkles, collagen vascular diseases such as cutaneous scleroderma, morphoea, lupus, rheumatoid arthritis, temporal arteritis, or hereditary collagen diseases, such as Ehlers-Danlos syndrome or Marfan's syndrome. 
     
     
         3 . The method of  claim 1 , wherein the biphasic lipid vesicle is formulated fora topical delivery. 
     
     
         4 . The method of  claim 3 , wherein the topical delivery comprises delivery to a skin or a mucosal membrane of the subject in need thereof. 
     
     
         5 . The method of  claim 3 , wherein the topical delivery comprises intradermal, transdermal, or transmucosal delivery. 
     
     
         6 . The method of  claim 1 , wherein the one or more compounds therapeutically effective in treating the skin condition related to excessive or defective collagen production are hydrophobic. 
     
     
         7 . The method of  claim 1 , wherein the one or more compounds therapeutically effective in treating the skin condition related to excessive or defective collagen production are hydrophilic. 
     
     
         8 . The method of  claim 1 , wherein the one or more compounds comprise small molecules, proteins, peptides, carbohydrates, nucleic acids, vaccine antigens, or plant extracts. 
     
     
         9 . The method of  claim 1 , wherein the biphasic lipid vesicle is biocompatible or biodegradable. 
     
     
         10 . The method of  claim 1 , wherein a dose of the one or more compounds therapeutically effective in treating the skin condition related to excessive or defective collagen production is based on one or more of: a pharmacodynamic property of the one or compounds, a mode of administration, age, health, or weight of the subject in need thereof, extent of a symptom, frequency of the treatment, type of concurrent treatment, or clearance rate of the one or more compounds in the subject in need thereof. 
     
     
         11 . The method of  claim 1 , wherein the biphasic lipid vesicle is administered to the subject in need thereof daily, weekly, or monthly. 
     
     
         12 . The method of  claim 1 , wherein the biphasic lipid vesicle is administered to the subject in need thereof for a duration sufficient to treat the skin condition. 
     
     
         13 . The method of  claim 1 , further comprising adjusting a dose of the one or more compounds or a frequency of administering the one or more compounds based on a pharmacodynamic property of the one or more compounds, a mode of administration, age, health or weight of the subject, an extent of a symptom, frequency of treatment, type of concurrent treatment, or clearance rate of the one or more compounds in the subject. 
     
     
         14 . The method of  claim 1 , wherein the biphasic lipid vesicle is administered using a transdermal delivery system. 
     
     
         15 . The method of  claim 14 , wherein the transdermal delivery system is a patch or a mask sheet. 
     
     
         16 . The method of  claim 14 , wherein the transdermal delivery system comprises a backing layer and a matrix layer disposed on the backing layer. 
     
     
         17 . The method of  claim 16 , wherein the matrix layer comprises the biphasic lipid vesicle composition, and wherein the matrix layer is configured for contacting skin. 
     
     
         18 . The method of  claim 1 , wherein the plurality of concentric lipid bilayers enclose an oil-in-water emulsion. 
     
     
         19 . The method of  claim 18 , wherein the plurality of concentric lipid bilayers, the oil-in-water emulsion, or both comprise one or more penetration enhancing agents. 
     
     
         20 . The method of  claim 19 , wherein the one or more penetration enhancing agents increases a quantity of the one or more compounds that absorbs into a quantity of skin by at least 10% relative to an otherwise same composition without the one or more penetration enhancing agents.