Compositions and methods for topical delivery of oligonucleotides

Abstract

The present invention relates to compositions and methods which enhance the delivery of oligonucleotides and other nucleosidic moieties via topical routes of administration. Preferred compositions include liposomes or penetration enhancers for the delivery of such moieties to dermal and/or epidermal tissue in an animal for investigative, therapeutic or prophylactic purposes.

1 . A pharmaceutical composition comprising an oligonucleotide, or salt thereof, admixed with a topical delivery agent comprising a penetration enhancing amount of polyoxyethylene, wherein said composition is formulated into a cream or emulsion. 
     
     
         2 . A pharmaceutical composition for topical delivery of an antisense oligonucleotide, comprising an oligonucleotide, or salt thereof, admixed with a penetration enhancing amount of a polyoxyethylene, wherein said composition is formulated into a cream or emulsion. 
     
     
         3 . The composition of  claim 1  or  2 , wherein said composition comprises about 1%-15% polyoxyethylene. 
     
     
         4 . The composition of  claim 1  or  2 , wherein said polyoxyethylene comprises polyoxyethylene (2) sorbitan monopalmitate (Tween 40), polyoxyethylene-40-stearate (polyoxy)-40-stearate), polyoxyethylene oleyl ether, polyoxyethylene-10-stearyl ether, polyoxyethylene-9-lauryl ether or polyoxyethylene-20-cetyl ether. 
     
     
         5 . The composition of  claim 1  or  2 , wherein at least one internucleoside linkage of the oligonucleotide is a modified internucleoside linkage. 
     
     
         6 . The composition of  claim 5 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         7 . The composition of  claim 1  or  2 , wherein at least one nucleoside of the oligonucleotide comprises a modified sugar. 
     
     
         8 . The composition of  claim 7 , wherein the modified sugar comprises a 2′-O-methoxyethyl. 
     
     
         9 . The composition of  claim 1  or  2 , wherein at least one nucleobase of the oligonucleotide is a modified nucleobase. 
     
     
         10 . The composition of  claim 9 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         11 . The composition of  claim 1  or  2 , wherein the oligonucleotide consists of 20 linked nucleosides.