具有吗啉侧基的聚氨基酸嵌段共聚物的控制释放研究

Preparation and pH-sensitive drug delivery study of mPEG-poly(morpholine propyl-asparagine)-poly(L-alanine)

通过大分子引发开环聚合和侧基改性,制备了一种侧链含有吗啉丙基的聚乙二醇-聚(吗啉丙基-天冬酰胺)-聚丙氨酸三嵌段共聚物。利用肿瘤细胞外、细胞内和正常组织pH值环境的差异,调节聚合物载药纳米粒子的结构和性能实现肿瘤部位靶向释放的目的。在水溶液中,此聚合物可自组装形成一种核-壳-冠型的3层共聚物胶束,其中疏水性的聚丙氨酸链段自聚集形成胶束的核,聚(吗啉丙基-天冬酰胺)链段形成具有pH值-响应性的壳层,用于包埋和释放药物,外围的聚乙二醇链段可以提供一个稳定的水合冠层,延长药物的体内循环时间。以阿霉素作为模型药物在自组装的过程中包埋到胶束内。研究发现,由于吗啉环在酸性条件下的质子化导致链段亲疏水性质发生明显变化,载药胶束的药物释放能力随环境pH值的降低药物的释放速率显著增加。

A novel biodegradable ABC type triblock copolymer mPEG-poly（benzyl L-aspartate）-P（L-Alanine） was synthesized by N-carboxyl anhydride ring-opening polymerization.Morpholine groups were tethered to the side chains of poly（L-asparagine） segments by aminolysis.mPEG-poly（morpholine propyl-asparagine）-poly（L-alanine） nanoparticles were prepared and used as carriers for tumor-targeting drug delivery.Doxorubicin（DOX） was encapsulated in the nanoparticles to explore the release profile.These DOX-loaded polymeric micelles exhibited rapid release of DOX from the micelles in weakly acidic environments but very slow release under physiological conditions（pH 7.4）.This is most likely due to protonation and a change in hydrophilicity of the morpholine groups in the poly（L-asparagine）.This new approach may serve as a promising platform to formulate targeted drug delivery systems.