Small Grants for Exploratory Research: Direct Microencapsulation of Proteins in Bioerodible Polymers Usinga Supercritical Fluid Anti-Solvent

小行星9321978 超临界流体抗溶剂（SAS）技术是一种新型的、有前途的制备高分子和生物材料小颗粒的方法。 我们建议探索直接微胶囊化的蛋白质颗粒在生物可侵蚀的聚合物基质SAS处理。 这些复合微粒可作为肽和蛋白质控释的理想载体。 我们最近已经证明了通过SAS生产干燥的、纯的和生物活性的多肽微粒的可行性。 我们现在建议研究的可行性，将这些多肽直接进入生物可蚀性聚合物基质，使用SAS处理。 待测试的模型系统是胰岛素和促黄体生成激素释放激素（蛋白质）、二甲亚砜（有机溶剂）、超临界CO2（抗溶剂）和生物可蚀聚酯（聚合物基质）。 将研究生物活性、肽释放速率和肽构象作为功能加工条件。 将研究SAS加工条件的变化，以便微调这些微粒的大小和分布，用于特定的药物递送系统。 如果成功的话，这项研究可以在一个单一的加工步骤中产生无溶剂的生物活性复合微粒。 这将代表在寻求递送治疗性肽和蛋白质的有效手段方面的突破。 ***

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. ***