生物可降解型石杉碱甲微球的研究

Study on biodegradable microspheres containing huperzine A

目的 制备能够在一个月甚至更长时间内缓释石杉碱甲的注射型生物可降解微球。方法 选用端基不封口的PLA或PLGA、采用简单的O／W乳化溶剂挥发法制备微球；详细考察了微球的形态、粒径及分布、载药量和包封率；用透析法测定微球的体外药物释放曲线。结果 成功地将石杉碱甲包裹入聚合物中；制得的微球表面光滑，但不同材料制得的微球内部结构不同，粒径全部小于250gm，粒径分布较窄，载药量的质量分数在4％～6．5％内，包封率的质量分数在45％～65％内，比用端基封口的聚合物制备的微球包封率高15倍以上；体外释药试验表明，载有石杉碱甲的3种微球能够在5～7周内缓释药物。结论 利用生物可降解型微球缓释石杉碱甲是可行的。

Objective To develop biodegradable microspheres for long term delivery of a potent acetyl cholinesterase inhibitor, huperzine A （HupA）, for at least one month. Methods Microspheres were success- fully prepared with specifical end-group uncapped poly （d,l-lactic acid） and poly （d, l-lactic-co-glycollic acid） using a simple O/W solvent evaporation method. The morphology, particle size and size distribution, drug loading capacity, drug entrapment efficiency （EE） and in vitro drug release were studied in detail. Results The prepared microspheres were smooth spherical spheres with different internal structure made from different type of polymers. The sizes of microspheres were all below 250μm with a narrow size distribution. The drug loading was between 4 %-6.5 % and the encapsulation efficiency （EE） was between 45 %-65 % which was 15 times more higher than the microspheres made from end-group capped PLA/PLGAs. The loaded microspheres could sustain release HupA for 5-7 weeks under in vitro condition. Conclusions It is feasible to deliver HupA for an extended time by using biodegradable microspheres.