Sol-Gel Phase-Reversible Hydrogel Templates and Uses Thereof

Abstract

Discrete microstructures of predefined size and shape are prepared using sol-gel phase-reversible hydrogel templates. An aqueous solution of hydrogel-forming material is covered onto a microfabricated silicon wafer master template having predefined microfeatures, such as pillars. A hydrogel template is formed, usually by lowering the temperature, and the formed hydrogel template is peeled away from the silicon master template. The wells of predefined size and shape on the hydrogel template are filled with a solution or a paste of a water-insoluble polymer, and the solvent is removed to form solid structures. The formed microstructures are released from the hydrogel template by simply melting the hydrogel template in water. The microstructures are collected by centrifugation. The microstructures fabricated by this method exhibit pre-defined size and shape that exactly correspond to the microwells of the hydrogel template. The method of preparing microstructures based on hydrogel templates is simple and can easily produce large quantities of the microstructures.

1 .- 33 . (canceled) 
     
     
         34 . A method of making drug-containing microparticles comprising:
 (a) filling a plurality of wells provided in a preformed, dissolvable hydrogel mold with a non-aqueous composition comprising: at least one drug, a non-water soluble polymer and non-aqueous solvent, which dissolvable hydrogel mold is formed of a sol-gel phase reversible hydrogel;   (b) solidifying the composition in the plurality of wells by evaporating the non-aqueous solvent, thereby forming microparticles; and   (c) harvesting the microparticles from the preformed dissolvable hydrogel mold by dissolving the hydrogel mold in an aqueous solution.   
     
     
         35 . The method of  claim 34 , wherein the drug is present in the microparticles in the range of about 1-80% by weight. 
     
     
         36 . The method of  claim 34 , wherein the drug is present in the microparticles in the range of about 5-50% by weight. 
     
     
         37 . The method of  claim 34 , wherein the microparticles have a diameter in the range of about 0.5 μm to about 100 μm. 
     
     
         38 . The method of  claim 34 , wherein the microparticles have a diameter in the range of about 1 μm to about 50 μm. 
     
     
         39 . The method of  claim 34 , wherein the harvesting step further comprises filtering and/or centrifugation of the microparticles from the aqueous solution. 
     
     
         40 . The method of  claim 34 , wherein the harvested microparticles are of homogeneous size. 
     
     
         41 . The method of  claim 34 , wherein the harvested microparticles are of homogeneous shape. 
     
     
         42 . The method of  claim 34 , wherein the non-water soluble polymer comprises PLGA. 
     
     
         43 . The method of  claim 34 , wherein the sol-gel phase reversible hydrogel comprises poly(vinyl alcohol).