Cai Mengtan, Zhu Kun, Qiu Yongbin, Liu Xinrong, Chen Yuanwei, Luo Xianglin
College of polymer science and engineering of Sichuan University, Chengdu 610065, China.
School of life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Colloids Surf B Biointerfaces. 2014 Apr 1;116:424-31. doi: 10.1016/j.colsurfb.2014.01.012. Epub 2014 Jan 27.
In order to prepare pH and redox sensitive micelles, amphiphilic copolymers of poly (epsilon-caprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) (PCL-PDEA) and disulfide-linked poly(ethyl glycol)-poly(epsilon-caprolactone) (mPEG-SS-PCL) were synthesized. The double-sensitive micelles were prepared simply by solvent-evaporating method with the mixed two copolymers. The pH sensitivity of the mixed micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic lighting scattering (DLS) and the redox sensitivity of the mixed micelles was testified by the change of micellar morphous observed by scanning electron microscope (SEM). In vitro drug release showed that drug-loaded mixed micelles (mass ratio 5:5) could achieve above 90% of drug release under low pH and reducing condition within 10h. Moreover, the drug-loaded mixed micelles (mass ratio 5:5) showed the largest cellular toxicity compared with other drug-loaded micelles, while blank mixed micelles exhibited no toxicity. These results meant that the mixed micelles composed by the two amphiphilic copolymers can enhance intracellular drug release. It is concluded that the newly developed mixed micelles can serve as a potential drug delivery system for anticancer drugs.
为了制备对pH和氧化还原敏感的胶束，合成了聚（ε-己内酯）-b-聚（甲基丙烯酸2-（二乙氨基）乙酯）（PCL-PDEA）和二硫键连接的聚（乙二醇）-聚（ε-己内酯）（mPEG-SS-PCL）两亲性共聚物。通过溶剂蒸发法简单地将两种共聚物混合制备双敏感胶束。通过动态光散射（DLS）测量胶束直径/直径分布的变化来确认混合胶束的pH敏感性，并通过扫描电子显微镜（SEM）观察胶束形态的变化来证明混合胶束的氧化还原敏感性。体外药物释放表明，载药混合胶束（质量比5:5）在低pH和还原条件下10小时内药物释放率可达90%以上。此外，与其他载药胶束相比，载药混合胶束（质量比5:5）表现出最大的细胞毒性，而空白混合胶束无毒性。这些结果表明，由两种两亲性共聚物组成的混合胶束可以增强细胞内药物释放。结论是，新开发的混合胶束可作为抗癌药物的潜在给药系统。
