生物降解多肽和蛋白质药物的控制释放研究

STUDIES ON CONTROLLED DELIVERY FOR PEPTIDE-PROTEIN DRUG WITH BIODEGRADABILITY

用具有生物降解性和血液相容性的聚乳酸 ( PLA)为载体材料 ,以牛血清白蛋白 ( BSA)为多肽 -蛋白质药物的模型化合物 ,分别用相分离法 ( PSM)和溶剂萃取法 ( SEM)制备出了平均粒径为 5 0～ 90 μm的 PLA/ BSA微球 .研究了不同制备方法 ,BSA用量 ,载体中明胶的加入及载体材料的构型对 BSA释放速度的影响 .结果表明 ,用 PSM和 SEM制备的 PLA/ BSA微球的包埋效率分别为 94 .1 %和 35 .2 % ,含明胶和不含明胶的 PLA/ BSA微球在 1 2 d内 BSA的累积释放量分别为 4 7.0 %和 84 .9% ,用上述两种方法制备的 PLA/ BSA微球均具有可控释放 BSA的功能 ,含明胶的 PLA/ BSA微球具有更长的

The biodegradable and blood compatible polylactic acid (PLA) microspheres for peptide and protein drug controlled delivery were prepared by encapsulating bovine serum albumin (BSA) in methylene chloride solution of PLA. The encapsulation was conducted by using a phase separation method (PSM) and a solvent extraction method(SEM). The average diameter of the PLA/BSA microspheres was about 50~90μm, BSA loading efficiency was 94.1% and 35.2% for PLA/BSA mincrospheres prepared by the phase separation method, and solvent extraction method, respectively. The results of BSA delivery tests indicated that PLA/BSA microspheres possessed controlled delivery characteristics. PLA/BSA microspheres contained gelatin possessed longer BSA delivery period than that of no gelatin ones, the cumulative amount of BSA was 47.0% and 84.9% in 12 days, respectively.$$$$