MEDICAL DEVICES FOR DELIVERY OF siRNA

Abstract

Disclosed are medical devices that incorporate siRNA. In addition to one or more siRNA constructs, devices include nanostructures fabricated on a surface to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Microneedles may be incorporated on devices. The pattern including nanostructures may be formed on the surface of the microneedles.

What is claimed is: 
     
         1 . A method for delivering an siRNA construct across a dermal barrier, the method comprising:
 penetrating the stratum corneum with a microneedle having a surface on which a plurality of nanostructures and a plurality of microstructures are arranged in a pattern that comprises a fractal and/or fractal-like geometry, wherein the nanostructures and microstructures project outward from the surface of the microneedle, and wherein the microneedle further contains a channel;   transporting an siRNA construct from a reservoir through the channel of the microneedle and across the stratum corneum.   
     
     
         2 . The method of  claim 1 , wherein the siRNA construct is transported across the stratum corneum at a steady concentration over a period of time. 
     
     
         3 . The method of  claim 1 , wherein the siRNA construct includes a duplexed region of between about 20 and about 30 pairs. 
     
     
         4 . The method of  claim 1 , wherein at least one strand of the siRNA construct includes a 3′ overhang of two or three nucleotides. 
     
     
         5 . The method of  claim 1 , wherein the siRNA construct comprises additional nucleotides or nucleotide analogues. 
     
     
         6 . The method of  claim 1 , wherein the siRNA construct includes insertions, deletions, or single point mutations compared to a portion of a targeted gene. 
     
     
         7 . The method of  claim 1 , wherein the siRNA construct is a single strand siRNA. 
     
     
         8 . The method of  claim 1 , wherein the siRNA comprises a ligand tethered to the siRNA. 
     
     
         9 . The method of  claim 8 , wherein the ligand is selected from the group consisting of a therapeutic modifier, a diagnostic compound, a reporter group, a crosslinking agent, a nucleobase, a lipophilic molecule, a protein, or combinations thereof. 
     
     
         10 . The method of  claim 1 , wherein the siRNA agent is incorporated into a delivery vehicle. 
     
     
         11 . The method of  claim 10 , wherein the delivery vehicle is a liposome. 
     
     
         12 . The method of  claim 1 , wherein the siRNA construct comprises a vector. 
     
     
         13 . The method of  claim 12 , wherein the vector is a viral vector. 
     
     
         14 . A method of forming a device for delivery of an siRNA construct across a dermal barrier, the method comprising:
 fabricating an array of microneedles;   fabricating a pattern of nanostructures on a surface of at least one of the microneedles, wherein the pattern comprises a fractal and/or fractal-like geometry; and   associating an siRNA construct with the microneedles such that the siRNA construct is in fluid communication with the microneedles.   
     
     
         15 . The method of  claim 14 , further comprising retaining the siRNA construct within a reservoir that is in fluid communication with the array of microneedles. 
     
     
         16 . The method of  claim 15 , wherein the reservoir is attached to a substrate upon which the array of microneedles are located. 
     
     
         17 . The method of  claim 15 , wherein the reservoir is removably connectable to the array of microneedles. 
     
     
         18 . The method of  claim 14 , wherein the pattern comprises a fractal dimension of greater than about 1. 
     
     
         19 . The method of  claim 18 , wherein the fractal dimension is between about 1.5 and 2.5. 
     
     
         20 . The method of  claim 14 , wherein the method further comprises fabricating a pattern of microstructures on the surface of at least one of the microneedles.