Notel长效微球制剂的制备和评价

Preparation and evaluation of Notel-loaded sustained-release microsphere

目的:制备并评价Notel聚乳酸-羟基乙酸共聚物(PLGA)长效缓释微球。方法:采用乳化-溶剂挥发法制备Notel缓释微球,以载药量、包封率、体外释放为评价指标,考察高分子材料、高分子溶液浓度、硬脂酸、不同pH的聚乙烯醇(PVA)溶液等因素对微球的影响,筛选最优处方并制备微球,考察大鼠药动学及对db/db小鼠的降血糖作用。结果:按最优处方制备的微球形态圆整,平均粒径为60μm,载药量12.5%,体外释药可达1个月。微球在大鼠体内1 h即有药物释放,第8天血药浓度达到峰值Cmax(52.96±3.20)ng·mL^(-1)并持续释放30 d。db/db小鼠的空腹血糖浓度在1个月内有效降低。结论:Notel缓释微球作为1个月长效制剂治疗2型糖尿病(T2DM)具有良好的开发前景。

OBJECTIVE To prepare and evaluate Notel-loaded poly（lactide-co-glycolide）（PLGA）microspheres designed for sustained release.METHODS Notel-loaded microspheres were obtained by emulsion-solvent evaporation method.Effects of factors including polymers,polymer concentration,stearic acid,PVA solution of different pH levels were analyzed on several dependent variables namely practical drug loading,encapsulation efficiency as well as in vitro drug release.Optimized formulation was selected,prepared and evaluated in terms of pharmacokinetics study in rats and glucose-lowering action in db/db mouse.RESULTS Surface morphology of optimized microspheres was regular,with an average particle size of 60μm and encapsulation efficiency of 12.5 %.The in vitro results exhibited a controlled release profile of Notel over a month.Pharmacokinetics study showed an immediate drug release in 1 h,peak value Cmax（52.96±3.20）ng·mL-1 on 8th day,sustained plasma drug release over 30 days in rats.Pharmacodynamics data revealed that fasting blood glucose in db/db mouse could be lowered effectively by Notel-loaded microspheres.CONCLUSION These results imply potential development of Notel-loaded biodegradable microspheres for management of type 2 diabetes mellitus for a month.