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

9321978脱比尼蒂超临界流体抗溶剂技术是一种新的、很有前途的形成聚合物和生物材料微粒的方法。我们建议探索通过SAS工艺将蛋白质颗粒直接微胶囊化到可生物侵蚀的聚合物基质中。这些复合微粒是控制释放多肽和蛋白质的理想载体。我们最近证明了用SAS生产干燥、纯净和具有生物活性的多肽微粒的可行性。我们现在建议研究使用SAS工艺将这些多肽直接结合到可生物侵蚀的聚合物基质中的可行性。被测试的模型系统是胰岛素和亮氨酸化激素释放激素(蛋白质)、二甲基亚砜(有机溶剂)、超临界二氧化碳(抗溶剂)和可生物侵蚀聚酯(聚合物基质)。生物活性、多肽释放速率和多肽构象将作为功能加工条件进行考察。将研究SAS加工条件的变化，以微调这些微粒的大小和分布，以用于特定的药物输送系统。如果成功，这项拟议的研究可以在单一工艺步骤中获得无溶剂、具有生物活性的复合微粒。这将代表着在寻求有效的传递治疗性多肽和蛋白质的方法方面的突破。***

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. ***