外水相中NaCl对S/O/W法制备的牛血清白蛋白PLGA缓释微球性质的影响  

Effect of NaCl in outer water phase on the characteristics of BSA-loaded PLGA sustained-release microspheres fabricated by a solid-in-oil-in-water emulsion technique

作　　者：周香莲[1] 贺进田[1] 周志涛[1] 马树芬[1] 姜杨 王英 

机构地区：[1]河北师范大学生命科学学院,河北石家庄050016 [2]华北制药集团金坦生物技术股份有限公司,河北石家庄050000

出　　处：《药学学报》2010年第8期1057-1063,共7页Acta Pharmaceutica Sinica

基　　金：河北省科技支撑计划项目(09276418D-3);河北省教育厅重点资助项目(200645);河北师范大学博士基金资助项目(L2005B23)

摘　　要：本文以牛血清白蛋白(bovine serum albumin,BSA)作为模式蛋白,用S/O/W乳化溶剂挥发法制备载有BSA的聚乳酸-羟基乙酸[poly(lactic-co-glycolic acid),PLGA]缓释微球,考察制备过程中影响微球性质的关键因素。用冷冻诱导相分离法制备BSA微粒,采用S/O/W乳化溶剂挥发法制备BSA微球。用光学显微镜、激光共聚焦显微镜和扫描电子显微镜观察了微滴和微球的形态结构,以Bradford法测定微球的蛋白含量,并研究微球中蛋白质的体外释放特性。结果发现,在制备微球过程中外水相中的NaCl会抑制微乳内外相的物质交换,进而影响了微球的结构和渗透性,使微球的包封率从60%提高到85%以上,突释率从70%降低到20%以下,粒径从103μm减小到62μm;并可抑制微乳内蛋白质微粒的再水化,保护包封过程中BSA的稳定性。在体外,BSA从微球中缓慢释放时间长达30天。The aim of this study is to investigate the critical factor affecting the properties of PLGA microspheres fabricated by a solid-in-oil-in-water （S/O/W） emulsion technique with BSA as a model protein. Prior to encapsulation,the BSA microparticles were fabricated by a modified freezing-induced phase separation method. The microparticles were subsequently encapsulated into PLGA microspheres by S/O/W emulsion method,then Motic BA200 biological microscope,confocal laser scanning microscope,scanning electron microscope were used to observe the structure of S/O/W emulsion and PLGA microspheres. The protein content extracted or released from BSA microspheres was measured by Bradford protein assay method. It was found that NaCl added in the outer aqueous phase effectively suppressed material exchange between the inner and outer phase of S/O/W emulsion. Then,the structure and permeability of obtained microspheres were influenced. As a result,with the increase of NaCl concentration in the outer aqueous phase,the encapsulation efficiency of microspheres significantly increased from 60% to more than 85%,the burst release of microspheres reduced from 70% to 20%,and the particle size decreased from 103 μm to 62 μm. Furthermore,the rehydration of encapsulated protein was also retarded and then integrity of BSA was successfully protected during encapsulation process. In vitro release test showed that BSA released from PLGA microspheres in a sustained manner for more than 30 days.

关 键 词：牛血清白蛋白 缓释 微球 乳酸-羟基乙酸共聚物 蛋白质稳定性 

分 类 号：R943[医药卫生—药剂学]