Polymeric micelles with citraconic amide as pH-sensitive bond in backbone for anticancer drug delivery
Polymeric micelles with citraconic amide as pH-sensitive bond in backbone for anticancer drug delivery
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以柠康酰胺作为主链 pH 敏感键的聚合物胶束用于抗癌药物输送
DOI：
10.1016/j.ijpharm.2014.05.010
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发表时间：
2014-08-25
影响因子：
5.8
通讯作者：
Gu, Zhongwei
中科院分区：
文献类型：
--
作者：
Cao, Jun;Su, Ting;Gu, Zhongwei
报道了一种新型的ph敏感聚合物胶束。合成了以柠檬酸酰胺为ph敏感键的甲氧基聚乙二醇-乙聚己内酯共聚物（mPEG-pH-PCL）。共聚物自组装成胶束包封抗癌药物阿霉素（DOX）。研究了DOX负载mPEG-pH-PCL胶束的形态、大小和粒径分布、药物释放谱及体外抗癌活性。结果表明，mPEG-pH-PCL胶束的平均粒径约为120 nm，载药量为6.8%，包封率为54.3%。当pH为5.5时，mPEG-pH-PCL胶束的平均直径和粒径分布显著增加。pH为5.5时胶束的药物释放速度明显快于pH为7.4时。激光共聚焦显微镜和流式细胞术检测表明，内体的弱酸性破坏了共聚物骨架中的柠檬酸酰胺键，引发了DOX的快速释放。载药mPEG-pH-PCL胶束的体外IC50均低于对HepG2和4T1癌细胞无ph敏感性的载药聚合物胶束。(C) 2014 Elsevier B.V.版权所有
A novel pH-sensitive polymeric micelle was reported. Methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) copolymer with citraconic amide as pH-sensitive bond was synthesized (mPEG-pH-PCL). The copolymers self-assembled into micelles to encapsulate anticancer drug doxorubicin (DOX). The morphology, size and size distribution, drug release profile and in vitro anticancer activity of the DOX loaded mPEG-pH-PCL micelles were studied. The results showed that the mean size of the micelles was around 120 nm, the drug loading content and encapsulation efficiency of the mPEG-pH-PCL micelles were 6.8% and 54.3%, respectively. The mean diameter and size distribution of the mPEG-pH-PCL micelles increased significantly when soaking in medium with pH 5.5. The drug release of micelles in pH 5.5 was much faster than that in pH 7.4. The confocal laser microscopy and flow cytometry measurements indicated that the weak acidity of endosomes broke the citraconic amide bonds in the copolymer backbones and triggered the fast release of DOX. The in vitro IC50 of the drug loaded mPEG-pH-PCL micelles was lower than that of drug loaded polymeric micelles without pH-sensitivity to both HepG2 and 4T1 cancer cells. (C) 2014 Elsevier B.V. All rights reserved.