9321978 Debenedetti The supercritical fluid antisolvent (SAS) technique is a novel and promising method of forming small particles of polymeric and biological materials. We propose to explore the direct microencapsulation of protein particles in a bioerodible polymeric matrix by SAS processing. These composite microparticles can be ideal vehicles for the controlled release of peptides and proteins. We have recently demonstrated the viability of producing dry, pure, and biologically-active polypeptide microparticles by SAS. We now propose to study the feasibility of incorporating these polypeptides directly into a bioerodible polymer matrix using SAS processing. Model systems to be tested are insulin and leutinising hormone - releasing hormone (proteins), dimethylsulfoxide (organic solvent), supercritical CO2 (antisolvent), and bioerodible polyesters (polymer matrix). The biological activity, peptide release rate, and peptide conformation will be investigated as a function processing condition. Changes in SAS processing conditions will be investigated so as to fine-tune the size and distribution of these microparticles for specific drug delivery systems. If successful, the proposed research can lead to solvent-free, biologically active composite microparticles in a single processing step. This would represent a breakthrough in the quest for efficient means of delivering therapeutic peptides and proteins. ***
