Coated Microstructures and Methods of Manufacture Thereof

Abstract

Coated microneedle devices and methods of making such devices are provided. In one aspect, a method for coating includes providing a microstructure having at least one surface in need of coating; and applying a coating liquid, which comprises at least one drug, to the at least one surface of the microstructure, wherein the surface energy of the coating liquid is less than the surface energy of the surface of the microstructure. The coating liquid may include a viscosity enhancer and surfactant. Microneedles having heterogeneous coatings, pockets, or both are also provided.

1 . A microneedle device for insertion of a drug into a biological tissue comprising:
 at least one microneedle having a base, a tip end, and a shaft portion therebetween; and   a coating on at least a portion of the surface of the at least one microneedle, the coating comprising at least one drug and a viscosity enhancer.   
     
     
         2 . The microneedle device of  claim 1 , wherein the coating further comprises a surfactant. 
     
     
         3 . The microneedle device of  claim 1 , wherein the viscosity enhancer comprises cellulose, a cellulose derivative, hyaluronic acid, xanthan gum, alginic acid, alginic acid derivative, polyvinylpyrollidone, acacia, guar gum, or a carbohydrate 
     
     
         4 . The microneedle device of  claim 1 , wherein the coating has a heterogeneous composition. 
     
     
         5 . The microneedle device of  claim 4 , wherein the coating comprises discrete particles. 
     
     
         6 . The microneedle device of  claim 4 , wherein the coating comprises two or more discrete layers. 
     
     
         7 . The microneedle device of  claim 4 , wherein the coating comprises at least two different phases. 
     
     
         8 . The microneedle device of  claim 1  wherein the shaft portion of the at least one microneedle comprises one or more pockets therein. 
     
     
         9 . The microneedle device of  claim 8 , wherein the coating is located substantially only in the one or more pockets. 
     
     
         10 . The microneedle device of  claim 8 , wherein the one or more pockets contain at least a portion of the coating and the coating comprises a liquid, gel, microparticles, or a combination thereof. 
     
     
         11 . The microneedle device of  claim 1 , wherein the coating further comprises a hydrogel. 
     
     
         12 . The microneedle device of  claim 11 , wherein the hydrogel coating is in a dried state. 
     
     
         13 . The microneedle device of  claim 1 , wherein all of the coating is adapted to come off of the microneedle following insertion into a biological tissue. 
     
     
         14 . The microneedle device of  claim 13 , wherein the coating is adapted to come off of the microneedle in fifteen minutes or less following insertion into a biological tissue. 
     
     
         15 . The microneedle device of  claim 14 , wherein the coating comprises drug dispersed in a matrix material which provides controlled release of the drug. 
     
     
         16 . The microneedle device of  claim 14 , wherein the drug is a hydrophobic molecule and the coating further comprises an amphiphilic material. 
     
     
         17 . The microneedle device of  claim 1 , wherein at least a portion of the coating is adapted to remain on the microneedle following insertion into a biological tissue. 
     
     
         18 . The microneedle device of  claim 17 , wherein substantially all of the coating is adapted to remain on the microneedle, which may be a sensor, following insertion into a biological tissue. 
     
     
         19 . The microneedle device of  claim 1 , further comprising a precoat material disposed between at least a portion of the at least one microneedle and the coating which comprises the drug. 
     
     
         20 . The microneedle device of  claim 19 , wherein the precoat material alters the surface energy of the microneedle. 
     
     
         21 . A microneedle device for insertion of a drug into a biological tissue comprising:
 at least one microneedle having a base, a tip end, and a shaft portion therebetween; and   a coating on at least a portion of the surface of the at least one microneedle, the coating comprising at least one drug,   wherein the coating has a heterogeneous composition.   
     
     
         22 . The microneedle device of  claim 21 , wherein the coating comprises discrete particles, two or more discrete layers, two different phases, or a combination thereof. 
     
     
         23 . The microneedle device of  claim 21 , wherein the shaft portion of the at least one microneedle comprises one or more pockets therein. 
     
     
         24 . A microneedle device for insertion of a drug into a biological tissue comprising:
 at least one microneedle having a base, a tip end, and a shaft portion therebetween; and   a coating on at least a portion of the surface of the at least one microneedle, the coating comprising at least one drug,   wherein the shaft portion of the at least one microneedle comprises one or more pockets therein.   
     
     
         25 . The microneedle device of  claim 24 , wherein the coating is located substantially only in the one or more pockets. 
     
     
         26 . The microneedle device of  claim 24 , wherein the one or more pockets contain at least a portion of the coating and the coating is in the form of a liquid, gel, microparticles, or a combination thereof. 
     
     
         27 . The microneedle device of  claim 1 , wherein the at least one microneedle is formed of stainless steel, titanium, or another metal. 
     
     
         28 . The microneedle device of  claim 27 , wherein the microneedles are electropolished. 
     
     
         29 . The microneedle device of  claim 1 , which comprises two or more of the microneedles. 
     
     
         30 . (canceled) 
     
     
         31 . A method for coating a microstructure comprising:
 providing a microstructure having at least one surface in need of coating; and   applying a coating liquid, which comprises at least one drug, to the at least one surface of the microstructure,   wherein the surface energy of the coating liquid is less than the surface energy of the surface of the microstructure.   
     
     
         32 - 46 . (canceled) 
     
     
         47 . A method for coating at least one microneedle comprising:
 providing a coating liquid disposed in one or more reservoirs, the coating liquid comprising at least one drug;   providing a physical mask having one or more apertures, each aperture having cross-sectional dimensions larger than the at least one microneedle to be coated;   aligning the at least one microneedle with at least one of the one or more apertures;   inserting the at least one microneedle through the aligned aperture and into the coating liquid, thereby coating at least a portion of the microneedle; and   removing the coated microneedle from the coating liquid and from the aperture.   
     
     
         48 . The method of  claim 47 , wherein the physical mask comprises a plurality of holes or slits which closely circumscribe each microneedle or a single row of microneedles. 
     
     
         49 . The method of  claim 48 , wherein the physical mask is in the form of a rigid plate secured to the reservoir. 
     
     
         50 . The method of  claim 47 , wherein the one or more reservoirs are defined in a secondary structure. 
     
     
         51 . The method of  claim 47 , wherein the physical mask has a plurality of the reservoirs defined in the physical mask. 
     
     
         52 . The method of  claim 47 , wherein the step of inserting the microneedle through the aligned aperture is done before moving both the physical mask and the microneedle in a manner to cause the microneedle to be dipped into the coating liquid. 
     
     
         53 . The method of  claim 47 , further comprising inserting the at least one microneedle into the same or a different coating liquid and then removing the microneedle from said same or different coating liquid. 
     
     
         54 . The method of  claim 47 , wherein the at least one microneedle comprises one or more pockets therein. 
     
     
         55 - 62 . (canceled) 
     
     
         63 . A method of making a microneedle device comprising:
 forming one or more microneedles from a metal; and   electropolishing the one or more microneedles to smooth the surfaces of the microneedles.   
     
     
         64 . (canceled) 
     
     
         65 . A microneedle patch comprising:
 an array two or more microneedles extending out of plane from a substrate; and   an adhesive material disposed between the two or more microneedles, the adhesive material comprising an adhesive suitable for removably securing the microneedle patch to a patient's skin.   
     
     
         66 - 67 . (canceled)