重组人生长激素缓释微球.Ⅰ.制备与体外释放研究

Biodegradable Microspheres Loaded with Recombinant Human Growth Hormone. Ⅰ. Study on Preparation and in vitro Release

采用复乳-溶媒蒸发法制备重组人生长激素(rhGH)可生物降解缓释微球,考察蛋白稳定剂泊洛沙姆407(F127)对rhGH体外释放的影响。利用均匀设计优化微球的处方和制备工艺,制得的rhGH-PLGA微球球形圆整,表面光滑致密,粒径均匀且具有较高的包封率和载药量。微球的体外释药行为呈先快后慢的两相释放模式,d30时含有F127的微球累积释药量约79%,较不含稳定剂的微球高22%。表明F127可通过抑制有机溶剂诱导的蛋白聚集而对rhGH起到稳定作用。

Biodegradable poly （lactic-co-glycolic acid） （PLGA） microspheres loaded with recombinant human growth hormone （rhGH） were prepared with water-in-oil-in-water double emulsification solvent evaporation process, and the effect of protein stabilizing agent---poloxamer 407 （F127） on its in vitro release was evaluated, The rhGH-PLGA microspheres, optimized utilizing uniform design, were smooth, dense and spherical, and possessed of a median diameter in a relatively narrow distribution, and had high encapsulation efficiency and drug loading. The in Vitro release of rhGH from the microspheres exhibited a biphase mode of rapid release followed by slow one, the cumulative amount of rhGH released from microspheres containing F127 in one month was approximately 79 %, which increased by 22 % over that from microspheres without protein stabilizing agent. The result implied that the stability of rhGH was improved by F127 during the process of microspheres preparation via preventing protein from aggregation induced by organic solvent.