Amphiphilic copolymers with pendent carboxyl groups for high-efficiency loading and controlled release of doxorubicin
Amphiphilic copolymers with pendent carboxyl groups for high-efficiency loading and controlled release of doxorubicin
复制标题
DOI：
10.1016/j.colsurfb.2015.04.066
复制
发表时间：
2015-08-01
影响因子：
5.8
通讯作者：
Zhuo, Ren-Xi
中科院分区：
文献类型：
--
作者：
Li, You-Mei;Jiang, Tao;Zhuo, Ren-Xi
本文以固定化猪胰脂肪酶（IPPL）为催化剂，在本体法合成了可生物降解的两亲性嵌段共聚物甲氧基聚乙二醇-b-聚（5-烯丙氧基-1，3-二氧六环-2-酮）（mPEG-b-PATMC）。巯基乙酸的巯基与PATMC链段的碳碳双键发生巯基-烯“点击”反应，得到侧链羧基修饰共聚物mPEG-b-PATMC-g-SCH 2COOH，用于肿瘤细胞对阿霉素（DOX）的高效载药和控释。结果表明，羧基改性和未改性的共聚物在水溶液中均能自组装形成纳米胶束，透射电镜（TEM）观察表明，DOX负载前后的胶束均呈球形分散，粒径为纳米级。与未修饰的共聚物相比，mPEG-b-PATMC-g-SCH 2COOH的侧链羧基修饰结构通过静电相互作用可显著提高载药量和包封率。体外释放研究显示mPEG-b-PATMC-g-SCH 2COOH的药物释放行为更加持续，没有初始突释，其可以通过离子强度和pH条件进一步调节。共聚焦激光扫描显微镜（CLSM）表明由mPEG-b-PATMC-g-SCH 2COOH递送的DOX的有效细胞摄取，而MU测定也显示对HeLa细胞的有效细胞毒性活性。(c)2015 Elsevier B. V.版权所有。
In this paper, biodegradable amphiphilic block copolymer based on methoxy poly(ethylene glycol)-b-poly(5-allyloxy-1,3-dioxan-2-one) (mPEG-b-PATMC) was successfully synthesized in bulk using immobilized porcine pancreas lipase (IPPL) as the catalyst. After thiol-ene "click" reactions occur between thiol group of thioglycolic acid and carbon-carbon double bonds of PATMC segments, the pendent carboxyl-modified copolymer mPEG-b-PATMC-g-SCH2COOH was obtained for high-efficiency loading and controlled release of doxorubicin (DOX) to cancer cells. Both the carboxyl-modified and unmodified copolymers could self-assemble to form nano-sized micelles in aqueous solution, while transmission electron microscopy (TEM) observation showed that the micelles dispersed in spherical shape with nano-size before and after DOX loading. Compared with the unmodified copolymer, the pendent carboxyl-modified structure in mPEG-b-PATMC-g-SCH2COOH could markedly enhance the drug-loading capacity and entrapment efficiency via the electrostatic interaction. The in vitro release studies showed more sustained drug release behavior of mPEG-b-PATMC-g-SCH2COOH without an initial burst, which could be further adjusted by the conditions of ionic strength and pH. Confocal laser scanning microscopy (CLSM) indicated efficient cellular uptake of DOX delivered by mPEG-b-PATMC-g-SCH2COOH, while MU assays also demonstrated potent cytotoxic activity against HeLa cells. (c) 2015 Elsevier B.V. All rights reserved.