School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia.
Drug Dev Ind Pharm. 2009 Nov;35(11):1364-74. doi: 10.3109/03639040902939213.
The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model.
The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin 30/70 as a reference product in streptozotocin-induced diabetic rats.
The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 microm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix.
The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.
本研究旨在制备能够至少控制胰岛素释放 1 周的载胰岛素聚乳酸-聚乙二醇微球，并评估其在链脲佐菌素诱导的糖尿病大鼠模型中的体内性能。
采用水包油包水双乳液溶剂蒸发技术制备微球。考察了不同制剂变量对产率、粒径、包封效率和体外释放曲线的影响。采用单剂量对优化制剂进行药代动力学研究，并与 Humulin 30/70 多剂量作为参考产品进行比较，在链脲佐菌素诱导的糖尿病大鼠中进行。
扫描电子显微镜下，胰岛素微球的优化制剂呈无孔、光滑表面、球形结构，平均粒径为 3.07μm，包封效率为理论载药量的 42.74%。体外胰岛素释放曲线呈双峰行为，初始突释是由于胰岛素吸附在微球表面，随后是聚合物基质中包封的胰岛素的缓慢持续释放。
优化的制剂和参比制剂在吸收程度上具有可比性。因此，这些微球可以作为新的控释给药系统。
