一种包埋蛋白质药物注射用多孔微球支架制备工艺及其体外释放研究

 目的制备能缓慢释放蛋白类药物的细胞生长支架并进行制备工艺优化。方法以牛血清白蛋白(BSA)为模型药物,制备含药聚乳酸-羟基乙酸共聚物(PLGA)微球作为组织工程支架。通过单因素考察实验,寻求影响微球表观形态及释放的主要因素,以正交设计法优化微球制备工艺。用扫描电镜观察微球表观形态,用增重法测定吸水率考察其孔隙率,并对微球粒径分布、体外释药等指标进行评价。结果制得组织工程用PLGA微球为中空疏松多孔结构。制备过程中的搅拌速度、PLGA浓度、均质乳化速度、发泡剂浓度、分散相PVA浓度以及内外水相体积比影响微球粒径、表面孔径大小、空隙率的大小。正交设计优化处方的微球平均粒径为435μm,表面孔穴平均孔径为23μm,30d累计释放可达70%。结论采用可生物降解的聚合物PLGA为载体材料制备的PLGA微球具有可注射、载荷细胞和缓慢释放蛋白类药物的特性,有望成为一种新型组织工程支架用于病变组织的修复和相关疾病的治疗。

Preparation of Protein Loaded Gas Foamed Open Porous Biodegradable Polymeric Microspheres Scaffold and Its Regulation of Protein Release

OBJECTIVE To prepare the BSA loaded gas foamed open porous biodegradable polymeric microspheres used as scaffold,to optimize the formulation,technics and release properties in vitro.METHODS The microspheres was prepared by double-emulsion method.Based on the result of single-factor selecting experiment,the formulations and the preparation methods were evaluated by orthogonal experiment method.RESULTS The microspheres was spongy and spherical with a mean diameter of 435 μm,the mean diameter of surface pores was 23 μm.Stirring rate,PVA and PLGA concentration,homogenizing power,the concentration of gas forming reagent showed effects on the surface pore diameter,density and particle size of microspheres.The encapsulation efficiency was 55%,and the accumulated releases of BSA exceeded 70%.CONCLUSION The tissue engineering scaffold is a good controled release system for protein.Microsphere scaffold is a better choice for a better immobilization and sustained release of the drug to enhance tissue regeneration or to cure the correlated disease.