粒细胞集落刺激因子缓释微球的研制  

Preparation of Sustained-release Microspheres Loaded with Granulocyte Colony-stimulating Factor

作　　者：张宇桐 朱琳[1] 吴飞[1] 金拓[1] ZHANG Yutong;ZHU Lin;WU Fei;JIN Tuo(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2023年第2期216-223,共8页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金项目(81872802)。

摘　　要：粒细胞集落刺激因子(1)半衰期短、易水解,临床应用时需多次注射,患者顺应性差。本研究分别通过高分子双水相乳液和双水相冷冻相分离法制备1-葡聚糖(DEX)颗粒预制剂,再通过S/O/W型乳化法制备多糖颗粒复合聚乳酸-羟基乙酸共聚物(PLGA)缓释微球,以提高1稳定性。结果显示,制备的2种1-DEX-PLGA缓释微球均粒度分布均一,包封率>70%,且能实现40 d内连续缓慢释放,最终释放量为75%~80%,并可使小鼠髓性白血病淋巴细胞株(NSF-60细胞)的增殖活性保持在85%以上。该研究表明,2种方法制备的1-DEX-PLGA缓释微球均可有效保护1活性,实现4周以上的平稳缓释,为制备蛋白缓释微球制剂提供了数据参考。Granulocyte colony-stimulating factor(1)has a short half-life and is easily hydrolyzed by enzymes,so that it usually requires multiple injections in clinical application,and shows poor patient compliance.In this study,prefabricated polysaccharide particles,1-dextran(DEX),were respectively prepared by the double aqueous emulsion and double aqueous lyophilization-induced phase separation methods,and then were loaded by poly(lactic-co-glycolic acid)(PLGA)microspheres through the S/O/W emulsion method to improve the stability of 1.The results showed that both two kinds of PLGA microspheres loaded with 1-DEX had homogenous particle size distribution,high encapsulation efficiency(>70%),75%-80%of total drug sustained-release in 40 days,and more than 85%of proliferative activity of mouse myeloid leukemia lymphocyte cell lines(NSF-60 cells).The PLGA microspheres loaded with 1-DEX by the two methods could improve the stability of 1 and realize sustained-release for over four weeks,providing a reference for preparing sustained-release microspheres loaded with protein drugs.

关 键 词：粒细胞集落刺激因子 双水相乳液 冷冻相分离 缓释 微球 蛋白活性 

分 类 号：R944.9[医药卫生—药剂学]