Tip-loaded microneedle arrays for transdermal insertion

Abstract

A method of forming a microneedle array can include forming a microneedle array that has one or more bioactive component. The microneedle array can include a base portion and plurality of microneedles extending from the base portion, and the one or more bioactive components are present in a higher concentration in the plurality of microneedles than in the base portion.

We claim: 
     
         1 . A dissolvable microneedle array for transdermal insertion into a patient comprising:
 one or more bioactive components;   a base portion; and   a plurality of microneedles extending from the base portion, wherein the one or more bioactive components are present in a higher concentration in the plurality of microneedles than in the base portion.   
     
     
         2 . The microneedle array of  claim 1 , wherein substantially all of the one or more bioactive components are located in the plurality of microneedles so that the base portion is substantially formed without any bioactive components contained therein. 
     
     
         3 . The microneedle array of  claim 2 , wherein the one or more bioactive components are locally concentrated in the plurality of microneedles so that the one or more bioactive components are generally present only in an upper half of respective microneedles in the microneedle array. 
     
     
         4 . The microneedle array of  claim 2 , wherein the plurality of microneedles are pre-formed to have a shape that comprises a first cross-sectional dimension at a top portion, a second cross-sectional dimension 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, wherein the one or more bioactive components are substantially concentrated in the area at or above the intermediate portion. 
     
     
         5 . The microneedle array of  claim 4 , wherein each microneedle generally tapers to a point above the intermediate portion and each microneedle generally tapers to a smaller cross-sectional dimension below the intermediate portion. 
     
     
         6 . The microneedle array of  claim 2 , wherein each microneedle comprises a plurality of layers of dissoluble biocompatible material. 
     
     
         7 . The microneedle array of  claim 6 , wherein the dissoluble biocompatible material is carboxymethylcellulose. 
     
     
         8 . The microneedle array of  claim 2 , wherein the one or more bioactive component comprises at least two different bioactive components. 
     
     
         9 . The microneedle array of  claim 8 , wherein the at least two different bioactive components are selected from the group consisting of a chemotherapeutic agent, an adjuvant, and a chemo attractant for a cancer chemo immunotherapy application. 
     
     
         10 . The microneedle array of  claim 9 , wherein the bioactive component comprises an antigen and an adjuvant for a vaccine application. 
     
     
         11 . The microneedle array of  claim 2 , wherein the one or more bioactive component comprises at least one viral vector. 
     
     
         12 . The microneedle array of  claim 11 , wherein the at least one viral vector comprises an adenovector. 
     
     
         13 . The microneedle array of  claim 12 , wherein the at least one viral vector comprises an adenovector. 
     
     
         14 . A method of fabricating a microneedle array comprising:
 applying a first solution of a dissoluble biocompatible material having one or more bioactive components contained therein to a microneedle array production mold;   applying a second solution of a dissoluble biocompatible material that does not contain one or more active components to the microneedle array production mold; and   drying the first and second solutions to form a solid microneedle array that comprises a base portion and a plurality of microneedles that extend from the base portion, wherein the one or more active components are substantially concentrated in the plurality of microneedles.   
     
     
         15 . The method of  claim 14 , wherein the one or more bioactive components are substantially concentrated in an upper half of respective microneedles of the microneedle array. 
     
     
         16 . The method of  claim 14 , wherein the one or more bioactive components of the first solution comprises at least one viral vector. 
     
     
         17 . The method of  claim 16 , wherein the at least one viral vector comprises an adenovector. 
     
     
         18 . The method of  claim 14 , further comprising
 forming a sheet of material having a plurality of layers formed by the application of at least the first and second solutions.   
     
     
         19 . The method of  claim 18 , wherein the method of forming the sheet of material comprises spatially distributing the first solution with the one or more bioactive component across the sheet of material, and wherein the spatially distributed one or more bioactive component is covered with the second solution of dissoluble biocompatible material before removing portions from the sheet of material to form the microneedle array. 
     
     
         20 . The method of  claim 18 , wherein the at least one bioactive component of the first solution or suspension comprises at least one viral vector.