Methods and Compositions for Transdermal Delivery of Nucleotides

Abstract

The present invention relates to formulations and related methods for transdermal delivery of nucleic acids. Specifically, the invention relates to a formulation containing lipids and an alcohol and which is capable of providing effective transdermal delivery of nucleic acid. The formulation can be used effectively to deliver nucleic acids for gene therapy and the treatment of disease.

1 . A composition for dermal delivery of nucleic acids, comprising:
 a) nucleic acids;   b) at least one neutral lipid; and   c) alcohol.   
     
     
         2 . A composition as in  claim 1 , wherein neutral lipids are selected from the group consisting of phosphatidylcholines such as 1,2-dioleoyl-snglycero-3-phosphoethanolamine, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine, and 1,2-dimyristoyl-glycero-3-phosphoethanolamine, stearic acid, palmitic acids, and combinations thereof. 
     
     
         3 . A composition as in  claim 1 , wherein the neutral lipids and the ethanol are present in the formulation at a ratio of neutral lipids to alcohol of from about 1.5:1 to about 4.5:0.5 by weight. 
     
     
         4 . A composition as in  claim 3 , the ratio of neutral lipids to alcohol is from about 1.8:1 to 3.5:1 by weight. 
     
     
         5 . A composition as in  claim 3 , the ratio of neutral lipids to alcohol is from about 2:1 to about 3:1 by weight. 
     
     
         6 . A composition as in  claim 3 , wherein the ratio of neutral lipids to alcohol is from about 2.5:1 to about 3:1 by weight. 
     
     
         7 . A composition as in  claim 1 , wherein the nucleic acids are present in amounts of from 50 μg/ml to 2000 μg/ml of the total composition. 
     
     
         8 . A composition as in  claim 1 , wherein the nucleic acids are present in amounts of from 75 μg/ml to 1500 μg/ml of the total composition. 
     
     
         9 . A composition as in  claim 1 , wherein the nucleic acids are present in amounts of from 100 to 1000 μg/ml of the total composition. 
     
     
         10 . A composition as in  claim 1 , wherein the nucleic acids are present in amounts of from about 400 to 800 μg/ml of the total composition. 
     
     
         11 . A composition as in  claim 1 , wherein the composition further includes a biocide. 
     
     
         12 . A composition as in  claim 12 , wherein the biocide is benzethonium chloride. 
     
     
         13 . A composition as in  claim 1 , wherein the composition further includes a permeation enhancer. 
     
     
         14 . A composition as in  claim 1 , wherein the permeation enhancer is selected from the group consisting of a quaternary ammonium salt, fatty acids, fatty acid esters, fatty alcohols, fatty acid esters of lactic acid or glycolic acid, glycerol triesters, glycerol diesters, glycerol monoesters, triacetin, short chain alcohols, urea, and mixtures thereof. 
     
     
         15 . A composition as in  claim 1 , wherein the permeation enhancer is a quaternary ammonium salt. 
     
     
         16 . A composition as in  claim 15 , wherein the quaternary ammonium salt is benzethonium chloride. 
     
     
         17 . A composition as in  claim 1 , wherein the nucleic acid is RNA. 
     
     
         18 . A composition as in  claim 17 , wherein the RNA is siRNA. 
     
     
         19 . A composition as in  claim 17 , wherein the RNA is shRNA. 
     
     
         20 . A composition as in  claim 17 , wherein the RNA is double stranded. 
     
     
         21 . A composition as in  claim 1 , wherein the nucleic acid is DNA. 
     
     
         22 . A composition as in  claim 1 , wherein the alcohol is selected from a group consisting of lower alcohols, ethanol, isopropyl alcohol, propanol, benzyl alcohol, methanol, other C 4 -C 10  mono-alcohols, and mixtures thereof. 
     
     
         23 . A composition as in  claim 22 , wherein the alcohol is ethanol.