骨形成蛋白微球温敏性凝胶复合系统的制备及释药特性研究  

Preparation of Recombinant Human Bone Morphogenetic Protein-2 Loaded Microspheres/Thermosensitive Hydrogels Complex and Its in Vitro Release Characteristics

作　　者：符旭东[1] 刘宏[1] 汤韧[1] 张孟佑[1] 

机构地区：[1]广州军区武汉总医院药剂科,武汉430070

出　　处：《中国药学杂志》2009年第13期1005-1008,共4页Chinese Pharmaceutical Journal

基　　金：湖北省科技攻关计划(2005AA301C38)

摘　　要：目的考察处方和制备工艺对人重组骨形成蛋白-2(rhBMP-2)微球释放度的影响,并比较rhBMP-2微球和rhBMP-2微球温敏性凝胶复合系统的体外释药特性。方法采用W/O/W型乳化溶剂挥发法以聚乳酸-羟基乙酸共聚物(PLGA)和端羧基聚乳酸-羟基乙酸共聚物(PLGA-COOH)为材料制备空白微球。通过吸附法制备rhBMP-2载药微球。以单甲基聚乙二醇-羟基乙酸共聚物(MPEG-PLGA)为材料制备凝胶。通过试管倒转法测定凝胶剂和微球凝胶剂的初始胶凝化温度(IGT),采用夹心法酶联免疫吸附法测定释药速度。结果20%的MPEG-PLGA凝胶和微球凝胶剂的IGT均在37℃左右,微球中药物呈现三相释药模式,而微球凝胶剂体外释药曲线符合Higuchi方程。采用PLGA-COOH制备的rhBMP-2微球,其突释明显小于以PLGA为材料制备的微球,增加内水相与油相的体积比、在内水相中加入氯化钠均可以在一定程度上减小突释。结论rhBMP-2微球温敏性凝胶复合系统可以减少药物突释,具有比微球剂更理想的体外释药特性。OBJECTIVE To examine the effects of formulation factors on in vitro release rate of recombinant human bone morphogenetic protein-2 （rhBMP-2） loaded microspheres and compare drug release profiles of microspheres and mierospheres/ thermosensitive hydrogels complex. METHODS Blank microspheres were prepared with W/O/W emulsion solvent evaporation method. RhBMP-2 loaded microspheres was prepared with absorption method. Thermosensitive hydrogels were prepared with MPEG-PLGA. Incipient gelation temperature （IGT） was measured by tube inversion method. Enzyme-linked immunosorbent assay was used to determine drug content and in vitro release rate. RESULTS The IGT of 20% MPEG-PLGA solution and microspheres/thermosensitive hydrogels complex was about 37 ℃.The profiles of rhBMP-2 microspheres were characterized by three phases, while the in vitro release profile of rhBMP-2 microspheres/thermosensitive hydrogels complex conformed to Higuchi equation. The amount of rhBMP-2 released from microspheres in the initial burst phase was decreased when PLGA-COOH was used to prepare microspheres instead of PLGA. The increase of the volume ratio of internal aqueous and the addition of NaCI to internal aqueous phase inhibitied the burst in initial release. CONCLUSION Rhbmp2-loaded microspheres/ thermosensitive hydrogels complex exerted a desirable release characteristics.

关 键 词：人重组骨形成蛋白-2 聚乳酸-羟基乙酸共聚物 单甲基聚乙二醇-羟基乙酸共聚物 温敏性凝胶 微球 突释 

分 类 号：R944[医药卫生—药剂学]