氧化还原敏感型胶束的构建和药物控释性能

Construction and Controlled Release Properties of Redox Responsive Micelles

采用3,3'-二硫代二丙酸、乙酰氯、N-Boc-乙醇胺、ε-己内酯、聚乙二醇单甲醚等为原料,通过分子内脱水、酰化、开环聚合、缩合等一系列反应制备了以聚乙二醇单甲醚(mPEG)为亲水端,聚己内酯(PCL)为疏水端,中间含有二硫键链接的两亲聚合物——mPEG-SS-PCL。通过核磁共振氢谱、傅里叶变换红外光谱对聚合物的结构进行表征;以阿霉素(DOX)为模型药物,探讨胶束载药性能和氧化还原敏感性能。并通过MTT法评价了聚合物的细胞毒性。研究结果表明,mPEGSS-PCL可自组装形成胶束,该胶束粒径分部均匀,外表圆整,粒径约为190 nm,其结构具有良好的氧化还原敏感性;胶束的载药量为10. 0%,载药稳定性良好,且具有显著的药物控制释放性;此外,胶束在细胞水平表现为良好的生物安全性。

The redox responsive amphiphilic polymer which contains disulfide linkage between hydrophilic block （methoxypolyethylene glycol, mPEG） and hydrophobic block（polycaprolactone, PCL） was prepared through a series of reactions including intramolecular dehydration, acylation, ring opening polymerization, condensation reaction, using 3, 3＇-dithiodipropionic acid, acetyl chloride, 2-boc-ethanolamine, ε-caprolactone, polyethylene glycol monomethyl ether as raw materials. The structure of polymers was characterized by 1H-NMR and FT-IR. Package load capacityand glutathione （GSH） sensitive properties were studied using doxorubicin （DOX） as model drug. The particle size and zeta potential of the micelles were investigated by laser particle size analyzer. The cytotoxicity of micelleS was evaluated by MTT method. The results show that mPEG-SS-PCL can be self-assembled into micelles with uniform size,, rounded surface. The particle size of micelles is about 190 nm., and the structure of the micelles is redox dependent. DOX loading efficiency of micelles with remarkable drug loading stability is 10.0%. The drug release process can be controlled by GSH level. Furthermore, micelles show good biological safety at cell level.