中文摘要：

采用两次乳化包埋技术制备了一种载蛋白的乳酸-乙醇酸共聚物/壳聚糖复式微球（Poly（lactide-co-glycolide）/chitosan微球,简称PLGA/chitosan微球）。先以复乳法（W/O/W）制备加载牛血清白蛋白（BSA）的PLGA微球,再以壳聚糖（Chitosan）为基体对PLGA微球进行包埋,用三聚磷酸钠（TPP）进行交联。制备中,改变内部PLGA基体的分子量制备了3种PLGA/chitosan微球以达到不同的释放动力学。采用扫描电镜（SEM）、激光粒度分析仪、傅里叶变换红外光谱法（FTIR）分别对PLGA/chitosan微球的形貌、平均粒径及表面物理化学特征进行了表征。进行了复式微球在体外的蛋白释放实验,同时检测了体外降解过程中环境pH值的变化。结果表明,PLGA/chitosan微球具有球中包埋球的复式结构。复式微球的载药率为6%~8%,微球平均粒径为40~60μm。该微球早期蛋白的突释较PLGA微球显著减少,释放周期大于75天。此外,PLGA/chitosan微球降解过程中,能维持孵育液的pH值在7~8之间,为人体可接受范围,是一种优异的蛋白缓释微球。

英文摘要：

Three kinds of poly（lactide-co-glycolide）/chitosan microspheres（abbreviated as PLGA/chitosan microspheres） were prepared with multiple emulsion technique.PLGA microspheres were prepared with the double emulsion method（W/O/W） based on PLGA as the matrix and bovine serum albumin（BSA） as the model protein.The PLGA microspheres were re-emulsified with chitosan solution containing BSA followed by cross-linking with sodium tripolyphosphate（TPP）.Three kinds of PLGA were used as the raw material of PLGA microspheres in order to modulate the release kinetics of the model protein.The microstructure,the size distribution and the physical chemical properties of the PLGA/chitosan microspheres were analyzed by scanning electron microscope（SEM）,laser scattering particle analyzer and fourier transform infrared（FTIR）,respectively.The release of BSA from PLGA/chitosan microspheres was monitored in PBS and compared with PLGA microspheres.Simultaneously,the pH changes of the PBS were measured during the incubation.The results show that PLGA/chitosan microspheres demonstrate a multinuclear and dual microsphere structure.The drug-loading rate and the mean size of the PLGA/chitosan microspheres were 6%~8% and 40~60 μm,respectively.The PLGA/chitosan microspheres have excellent release curves with a less burst release and a longer than 75 days release.The degradation of PLGA/chitosan microspheres does not induce acidic environment as indicated by a pH value of 7~8 throughout the degradation.The PLGA/chitosan microspheres are excellent vehicles suitable for the proteins.