Preparation and use of photopolymerized microparticles

Abstract

Methods of forming crosslinked polymer particles in situ from polymer precursors such as monomers or oligomers, comprising exposing a composition comprising at least one polymer precursor, a solvent or solvent mixture, and an antisolvent or antisolvent mixture to photoradiation under conditions whereby particles are formed are provided. The polymer precursor may be photosensitive, or a separate polymerization initiator may be used. In a preferred embodiment, the polymer precursor is insoluble in the antisolvent or antisolvent mixture and the solvent or solvent mixture is soluble in the antisolvent or antisolvent mixture at the concentrations used. Crosslinked polymer particles and crosslinked polymer particles comprising a polymer and a bioactive material are also provided. The polymer may be erodable, and the polymer particles formed may be used in a variety of applications, including controlled release of bioactive materials such as drugs. Polymer particles formed using the methods of the invention have low residual solvent levels and high additive encapsulation efficiencies. The processes of the invention allow control of particle size and morphology, use low operating temperatures and are useful for efficient bulk production.

1 . Crosslinked polymer particles, wherein the particles are between 0.1 and 200 microns in diameter and have a network mesh size between about 10 and about 500 Angstroms.  
     
     
         2 . The particles of  claim 1 , wherein the polymer is selected from the group consisting of: vinyl acetates, vinyl pyrrolidones, vinyl ethers, olefins, styrenes, vinyl chlorides, ethylenes, acrylates, methacrylates, nitriles, acrylamides, maleates, epoxies, epoxides, lactones, ethylene oxides, ethylene glycols, ethyloxazolines, amino acids, saccharides, proteins, anhydrides, amides, carbonates, phenylene oxides, acetals, sulfones, phenylene sulfides, esters, fluoropolymers, imides, amide-imides, etherimides, ionomers, aryletherketones, amines, phenols, acids, benzenes, cinnamates, azoles, silanes, chlorides, and epoxides.  
     
     
         3 . The particles of  claim 1 , wherein the polymer comprises a plurality of converted carbon-carbon double bond functional groups.  
     
     
         4 . The particles of  claim 3 , wherein the conversion of the carbon-carbon double bonds is between about 20% and about 100%.  
     
     
         5 . The particles of  claim 3 , wherein the conversion of the carbon-carbon double bonds is between about 70% and about 100%.  
     
     
         6 . The particles of  claim 1 , wherein the polymer comprises a plurality of converted acrylate groups.  
     
     
         7 . The particles of  claim 1 , wherein the polymer is poly(ethylene glycol) (PEG) diacrylate.  
     
     
         8 . The particles of  claim 1 , wherein the polymer comprises a plurality of converted methacrylate groups.  
     
     
         9 . The particles of  claim 1 , wherein the polymer is methacrlyated sebacic anhydride (MSA)  
     
     
         10 . The particles of  claim 1 , wherein the polymer is a copolymer.  
     
     
         11 . The particles of  claim 1 , wherein the polymer is a copoly(PEG-b-D,L PLA) diacrylate.  
     
     
         12 . The particles of  claim 1 , wherein the polymer is biodegradable.  
     
     
         13 . The particles of  claim 1 , wherein the particles comprise less than about 1% of residual solvent.  
     
     
         14 . The particles of  claim 1 , wherein the polymer is a functionalized polymer having at least one unreacted reactive group comprising a carbon-carbon double bond.  
     
     
         15 . The particles of  claim 3 , wherein the reactive group is selected from the group consisting of acrylates, methacrylates, alkenes and alkynes.  
     
     
         16 . Crosslinked polymer particles wherein the particles are between 0.1 and 200 microns in diameter, the polymer comprises a plurality of converted carbon-carbon double bond functional groups, and the conversion of the carbon-carbon double bonds is between about 20% and about 100%.  
     
     
         17 . Crosslinked polymer particles wherein a bioactive material is encapsulated within the polymer.  
     
     
         18 . The particles of  claim 17  wherein the encapsulation efficiency of the bioactive material is above about 60%.  
     
     
         19 . The particles of  claim 17  wherein the polymer comprises a plurality of converted acrylate groups.  
     
     
         20 . The particles of  claim 17  wherein the polymer comprises a plurality of converted methacrylate groups.  
     
     
         21 . The particles of  claim 17  wherein the polymer is selected from the group consisting of: poly(ethylene glycol) (PEG) diacrylate, methacrylated sebacic anhydride (MLA), and copoly(PEG-b-D,L-PLA) diacrylate.  
     
     
         22 . The particles of  claim 17  wherein the bioactive material has a molecular weight less than about 1000 Da.  
     
     
         23 . The particles of  claim 17  wherein the bioactive material is selected from the group consisting of: tacrine, erythromycin, erythromycin estolate, and erythromycin ethylsuccinate.