氢氧化镁的载入量和粒径对艾塞那肽PLGA微球体外释放行为的影响

Effects of Loading and Particle Size of Magnesium Hydroxide on in vitro Drug Release Behavior of Exenatide-loaded PLGA Microspheres

使用艾塞那肽为模型药物、聚乳酸-羟基乙酸共聚物(PLGA)为载体,加入不同粒径和用量的氢氧化镁为抗酸剂,采用s/o/w型乳化-溶剂挥发法制备长效微球。从微球表面形貌、粒度分布、艾塞那肽和氢氧化镁的载入量、累积释放率、释放介质pH值变化等角度表征所得微球的体外释放过程。结果显示,微球中氢氧化镁的载入量对延长药物释放时间具有显著作用。随着氢氧化镁载入量的增加,PLGA的酸降解程度受到抑制,微球溶蚀、皱缩、塌陷、破裂等状态发生的时间向后推移,对开发长效持续释放微球具有指导意义;未观察到氢氧化镁粒径对微球释药行为产生明显影响。因此,氢氧化镁抗酸剂在长效微球制剂的开发方面具有良好的应用潜力。

The long-acting microspheres with exenatide as model drug were prepared by solid-in-oil-in-water emulsion-solvent evaporation method with poly(lactic-co-glycolic acid)(PLGA)as a carrier and magnesium hydroxide as an antacid.Through adding different amounts of magnesium hydroxide with different particle sizes,the effect of magnesium hydroxide on sustained-release behavior of exenatide from the microspheres was investigated.In vitro release process of the prepared microspheres was characterized by scanning electron microscopy,particle size distribution,loading levels of exenatide and magnesium hydroxide,cumulative drug release and pH change of release medium.In vitro release test showed that the loading level of magnesium hydroxide had a significant effect on prolongation of drug release.With the increasing of magnesium hydroxide loading level,the degradation degree of PLGA was inhibited and the processes of microspheres erosion,shrinkage,collapse and rupture were also delayed.It had a guiding significance in development of long-acting microspheres.No obvious effects of particle size of magnesium hydroxide on release behavior of the microspheres were observed.Therefore,antacid magnesium hydroxide described in this study has a good application potential in development of long-acting microspheres.