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

超临界流体抗溶剂（SAS）技术是一种形成聚合物和生物材料小颗粒的新颖而有前途的方法。我们提出利用SAS处理技术在生物可降解聚合物基质中直接微胶囊化蛋白质颗粒。这些复合微粒是控制多肽和蛋白质释放的理想载体。我们最近证明了用SAS生产干燥、纯净和生物活性多肽微粒的可行性。我们现在建议研究使用SAS处理将这些多肽直接纳入生物可降解聚合物基质的可行性。待测试的模型系统包括胰岛素和亮氨酸激素释放激素（蛋白质）、二甲基亚砜（有机溶剂）、超临界二氧化碳（抗溶剂）和生物可降解聚酯（聚合物基质）。生物活性、肽释放率和肽构象将作为功能加工条件进行研究。将研究SAS处理条件的变化，以便微调这些微粒的大小和分布，用于特定的药物输送系统。如果成功，这项研究可以在一个单一的处理步骤中产生无溶剂、生物活性的复合微粒。这将代表着在寻找有效途径递送治疗性肽和蛋白质方面的一个突破。＊＊＊

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. ***