ABSTRACT

This work aims to study the construction of reverse aspirin-loaded micelles prepared from amphiphilic PEG-PLA-SA triblock copolymers and the optimization of the preparation process. Using polyethylene glycol (PEG) as the initiator, ring-opening polymerization of L-lactide (L-LA) was used to prepare PEG-PLA diblock copolymers. Final product PEG-PLA-SA triblock copolymers were prepared by the reaction of stearic acid (SA) and PEG-PLA catalyzed by 4-dimethylaminopyridine (DMAP) and N,N’-Dicyclohexylcarbodiimide (DCC). Fourier transform infrared spectrometer (FT-IR) was used to characterize the product structure. PEG-PLA-SA triblock copolymers self-assembled in toluene/ethanol/water system to form reverse micelles, which could encapsulate aspirin into a hydrophilic core. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to determine the size and morphology of reverse micelles. The results showed that the reverse micelles are spherical, with a particle size of less than 70 nm. Response surface analysis method was applied to optimize the preparation process of PEG-PLA-SA. In vitro drug release was achieved by embedding reverse aspirin-loaded micelles in the biocompatible membrane in phosphate buffer saline (PBS) at 37°C. In the first 8 h, the drug release rate of the triblock copolymers was slower than that of the diblock copolymers. After 8 h, the drug release rate of both tended to be flat. The stability of aspirin-loaded reverse micelles was studied through accelerated test. These results indicate that reverse micelle PEG-PLA-SA may be a promising carrier for hydrophilic drugs like aspirin.

摘要

这项工作旨在研究由两亲性PEG-PLA-SA三嵌段共聚物制备的反向加载阿司匹林的胶束的构建以及制备工艺的优化。以聚乙二醇（PEG）为引发剂，使用L-丙交酯（L-LA）的开环聚合反应来制备PEG-PLA二嵌段共聚物。最终产物PEG-PLA-SA三嵌段共聚物是通过硬脂酸（SA）和PEG-PLA在4-二甲基氨基吡啶（DMAP）和N，N'-二环己基碳二亚胺（DCC）的催化下反应制备的。使用傅立叶变换红外光谱仪（FT-IR）表征产品结构。PEG-PLA-SA三嵌段共聚物在甲苯/乙醇/水系统中自组装，形成反胶束，可将阿司匹林包裹在亲水核中。动态光散射（DLS）和透射电子显微镜（TEM）用于确定反胶束的大小和形态。结果表明反胶束为球形，粒径小于70 nm。采用响应面分析法优化了PEG-PLA-SA的制备工艺。体外药物释放是通过在37°C的磷酸盐缓冲盐水（PBS）中将反阿司匹林负载的胶束嵌入生物相容性膜中来实现的。在最初的8小时内，三嵌段共聚物的药物释放速率比二嵌段共聚物的药物释放速率慢。8小时后，两者的药物释放速率趋于平稳。通过加速试验研究了阿司匹林负载的反胶束的稳定性。