乳化溶剂挥发法制备重组人血管内皮抑制素缓释微球  

Encapsulation of recombinant human endostatin using a W/O/O phase separation method

作　　者：许向阳[1] 李玲[2] 华苏[2] 胡一桥[1] 

机构地区：[1]南京大学生命科学学院,南京210008 [2]江苏先声药物研究有限公司,南京210042

出　　处：《中国新药杂志》2010年第4期343-347,共5页Chinese Journal of New Drugs

摘　　要：目的:制备重组人血管内皮抑制素(恩度)缓释微球,并对微球理化性质及体外释放行为进行初步考察。方法:采用乳化溶剂挥发法(W/O/O)制备恩度载药微球;对微球载药量、粒径、突释、体外释放速率及降解行为进行考察,同时利用凝胶电泳初步评价体外释放过程中恩度的完整性。结果:增加聚乳酸-羟基乙酸嵌段共聚物(PLGA)中羟基乙酸的比例、提高PLGA浓度、降低内水相体积、提高理论载药量均增加微球载药能力;降低内水相体积、提高分散速度均减小突释。增加PLGA中羟基乙酸的比例,30 d时累积释放可增加到65%。降解实验说明释放初期微球主要以扩散方式释放恩度,释放后期主要表现为微球的降解。凝胶电泳结果表明微球制备过程对蛋白质聚集性的影响不大。结论:用PLGA作为载体材料制备微球,可以延缓恩度的释放。Objective：To prepare recombinant human endostatin（Endostar） loaded sustained release microspheres and to evaluate the characterization and release behavior of microspheres.Methods：Endostar loaded microspheres were prepared by W/O/O phase separation method.The characters of microspheres,such as drug loading,size and burst release were evaluated.The in vitro release behavior was studied and the degradation was observed.The integrity of Endostar released from microsphere was detected by SDS-PAGE.Results：The increase of the percent of glycolic acid led to increase the drug loading and release rate.By decreasing internal phase volume and increasing theoretical drug loading and the concentration of poly（D,L,lactic-co-glycolic acid）（PLGA）,Endostar was easier to encapsulated into microspheres.Burst release decreased with increasing homogenization speed but increased with internal phase volume.The accumutive release rate could be increased to 65% at day 30 by increasing the proporation of glycolic acid in PLGA.The in vitro release of Endostar from the microspheres dependented on diffusion of drug through the matrix in the early stage and degradation of PLGA in the later stage.The SDS-PAGE study indicated that Endostar encapsulated did not show any aggregation.Conclusion：Endostar can be encapsulated in microspheres to yield a sustained release when using PLGA polymers as carrier materials.

关 键 词：重组人血管内皮抑制素 聚乳酸-羟基乙酸嵌段共聚物 扫描电镜 凝胶电泳 释放 

分 类 号：R943.41[医药卫生—药剂学] R979.1[医药卫生—药学]