Polymeric Microneedles and Rapid Additive Manufacturing of the Same

Abstract

The invention generally relates to microneedle devices, methods of making same, pharmaceutical compositions comprising same, and methods of treating a disease comprising administering same. Specifically, the disclosed microneedle devices comprise a plurality of biocompatible microneedles having one or more of: (i) a curved, discontinuous, undercut, and/or perforated sidewall; (ii) a sidewall comprising a breakable support; and (iii) a cross-section that is non-circular and non-polygonal. The microneedles may also be tiered. Alternatively, the microneedles may be tiered. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

1 . A microneedle device comprising:
 (a) a backing; and   (b) a plurality of biocompatible microneedles projecting from the backing, and wherein the microneedles comprise one or more of:
 (i) a curved, discontinuous, undercut, and/or perforated sidewall; 
 (ii) a sidewall comprising a breakable support; and 
 (iii) a cross-section that is non-circular and non-polygonal, 
 and/or wherein the microneedles are tiered, and wherein the microneedles have a cross-sectional width that varies in both dimensions along at least a portion of their length. 
   
     
     
         2 . The device of  claim 1 , wherein the microneedles have a tip diameter of less than about 10 micrometers. 
     
     
         3 . The device of  claim 1 , wherein the backing and the microneedles comprise the same material. 
     
     
         4 . The device of  claim 1 , wherein the backing and the microneedles comprise different materials. 
     
     
         5 . The device of  claim 1 , wherein the microneedles comprise a curved, discontinuous, or undercut sidewall. 
     
     
         6 . The device of  claim 1 , wherein the microneedles comprise a perforated sidewall. 
     
     
         7 . The device of  claim 6 , wherein the sidewall is physically perforated. 
     
     
         8 . The device of  claim 6 , wherein the sidewall is chemically perforated. 
     
     
         9 . The device of  claim 1 , wherein the sidewall comprises a breakable support. 
     
     
         10 . The device of  claim 1 , wherein the cross-section is non-circular and non-polygonal. 
     
     
         11 . The device of  claim 1 , wherein the microneedles are hollow. 
     
     
         12 . The device of  claim 1 , wherein the microneedles are biodegradable and/or bioabsorbable. 
     
     
         13 . The device of  claim 1 , wherein the microneedles comprise a biodegradable and/or bioabsorbable polymer. 
     
     
         14 . The device of  claim 1 , wherein the microneedles comprise a therapeutic agent. 
     
     
         15 . A method of delivering a therapeutic agent to a subject, the method comprising administering to the subject a microneedle device comprising:
 (a) a backing;   (b) a plurality of biocompatible microneedles projecting from the backing, wherein the microneedles comprise a therapeutic agent and one or more of:
 (i) a curved, discontinuous, undercut, or perforated sidewall; 
 (ii) a sidewall comprising a breakable support; and 
 (iii) a cross-section that is non-circular and non-polygonal, 
 and/or wherein the microneedles are tiered, thereby delivering the therapeutic agent. 
   
     
     
         16 . The method of  claim 15 , wherein the therapeutic agent comprises a protein therapeutic, a small molecule therapeutic, a vaccine antigen, or an antigenic fragment thereof 
     
     
         17 . A method of making a microneedle device, the method comprising the steps of:
 (a) providing a build elevator and an optically transparent build surface, wherein the build elevator and the build surface together define a build region there between, wherein the build surface is permeable to a polymerization inhibitor, and wherein the build surface is in fluid communication with a source of the polymerization inhibitor;   (b) filling the build region with a polymerizable liquid;   (c) irradiating the build region through the build surface to produce a solid polymerized region in the build region;   (d) forming or maintaining a liquid film release layer between the solid polymerized region and the build surface, wherein the liquid film release layer comprises the polymerizable liquid, and wherein the polymerization of the liquid is inhibited by the polymerization inhibitor; and   (e) advancing the build elevator away from the build surface to create a subsequent build region between the solid polymerized region and the build surface while concurrently filling the subsequent build region with the polymerizable liquid,   wherein the device comprises:   (f) a backing; and   (g) a plurality of biocompatible microneedles projecting from the backing, wherein the microneedles comprise one or more of:
 (i) a curved, discontinuous, undercut, or perforated sidewall; 
 (ii) a sidewall comprising a breakable support; and 
 (iii) a cross-section that is non-circular and non-polygonal, 
   and/or wherein the microneedles are tiered,   thereby making the microneedle device.   
     
     
         18 . The method of  claim 17 , wherein irradiating is via actinic radiation. 
     
     
         19 . The method of  claim 17 , wherein advancing comprises moving the build elevator vertically away from the build surface. 
     
     
         20 . The method of  claim 17 , wherein the microneedle device is formed in less than about 30 minutes.