Dissolvable microneedle arrays for transdermal delivery to human skin

Abstract

A method of forming a microneedle array can include forming a sheet of material having a plurality of layers and micromilling the sheet of material to form a microneedle array. At least one of the plurality of layers can include a bioactive component, and the microneedle array can include a base portion and plurality of microneedles extending from the base portion.

We claim: 
     
         1 . A method of forming a microneedle array, comprising:
 forming a sheet of material having a plurality of layers, at least one of the plurality of layers comprising a bioactive component; and   micromilling the sheet of material to form a microneedle array, the microneedle array comprising a base portion and plurality of microneedles extending from the base portion.   
     
     
         2 . The method of  claim 1 , wherein the plurality of layers comprise a dissoluble biocompatible material. 
     
     
         3 . The method of  claim 2 , wherein the dissoluble biocompatible material is carboxymethylcellulose. 
     
     
         4 . The method of  claim 3 , wherein the act of forming a sheet of material having a plurality of layers comprises:
 providing a layer of a hydrogel of carboxymethylcellulose to create a base layer, the base layer having a substantially uniform thickness;   drying the base layer until the base layer is substantially solid;   providing one or more active layers above the base layer, the one or more active layers having a substantially uniform thickness and comprising a hydrogel of carboxymethylcellulose and a bioactive component; and   drying the one or more active layers until the one or more active layers are substantially solid.   
     
     
         5 . The method of  claim 1 , wherein the act of micromilling the sheet of material comprises:
 micromilling the sheet of material to form a plurality of microneedles that are generally pyramidal in shape.   
     
     
         6 . The method of  claim 1 , wherein the act of micromilling the sheet of material comprises:
 micromilling the sheet of material to form a plurality of pillar microneedles, each pillar microneedle comprising a generally pyramidal section at a top portion of the microneedle and a generally rectangular section at a bottom portion of the microneedle.   
     
     
         7 . The method of  claim 6 , wherein the act of micromilling the sheet of material further comprises:
 micromilling a fillet portion on each microneedle, the fillet portion being located at the area where the microneedle contacts the base portion of the microneedle array.   
     
     
         8 . The method of  claim 1 , wherein the act of micromilling the sheet of material comprises:
 forming the microneedle array so that each microneedle comprises a first cross-sectional dimension at a top portion, a second cross-sectional area at a bottom portion, and a third cross-sectional dimension at an intermediate portion, wherein the intermediate portion is located between the top portion and the bottom portion, and the third cross-sectional dimension is greater than the first and second cross-sectional dimensions.   
     
     
         9 . The method of  claim 1 , wherein the bioactive component comprises two or more different bioactive components. 
     
     
         10 . The method of  claim 9 , wherein the bioactive component comprises at least one antigen and at least one adjuvant for a vaccine application. 
     
     
         11 . A microneedle array formed by the process of  claim 1 . 
     
     
         12 . A method comprising:
 forming a sheet of material having a plurality of layers, at least one of the plurality of layers comprising a bioactive component; and   removing portions from the sheet of material until a microneedle array is formed having a base portion and plurality of microneedles extending from the base portion,   wherein the removal of portions from the sheet array comprises forming the microneedle array so that each microneedle comprises a first cross-sectional dimension at a top portion, a second cross-sectional area at a bottom portion, and a third cross-sectional dimension at an intermediate portion, the intermediate portion being located between the top portion and the bottom portion, and the third cross-sectional dimension being greater than the first and second cross-sectional dimensions.   
     
     
         13 . The method of  claim 12 , wherein the act of removing portions from the sheet of material comprises micromilling the sheet of material to form the plurality of microneedles. 
     
     
         14 . The method of  claim 13 , further comprising:
 micromachining a fillet portion on each microneedle, the fillet portion being located at the area where the microneedle contacts the base portion of the microneedle array.   
     
     
         15 . The method of  claim 12 , wherein the bottom portion tapers inward on all sides to the second cross-sectional dimension. 
     
     
         16 . The method of  claim 15 , wherein respective microneedles generally taper from the intermediate portion to a point above the intermediate portion and generally taper from the intermediate portion to a smaller cross-sectional dimension adjacent an area where the microneedle contacts the base portion.