Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yu-Hang-Tang Road, Hangzhou, 310058, China.
Nanomedicine (Lond). 2010 Feb;5(2):193-208. doi: 10.2217/nnm.09.108.
Delivery of doxorubicin could be achieved by a novel micellar system based on beta-cyclodextrin-centered star-shaped amphiphilic polymers (sPEL/CD). This study specifically explored the effect of polylactide segments in sPEL/CD on various micelle properties, such as the critical micelle concentration, size, drug loading, cytotoxicity and drug resistance reversing effect.
The sPEL/CD was synthesized by the arm-first method. The critical micelle concentrations of polymeric micelles were determined by fluorescence spectrophotometry using pyrene as a probe. The oil/water method was applied to prepare doxorubicin-loaded micelles. 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide, confocal laser-scanning microscopy and flow cytometry were used to examine cell cytotoxicity and cellular uptake of the doxorubicin-loaded micelles. Finally, rhodamine-123 cellular uptake was determined to evaluate the polymer action on MCF-7 and MCF-7/ADR cells.
All polymers exhibited low cytotoxicity and their micelles had a desirable release-acceleration pH (pH 5.0) for cytoplasmic drug delivery. With the introduction of polylactide into the polymer, the micelle critical micelle concentration can be effectively decreased and the drug-loading content was enhanced. Most importantly, the drug resistance of MCF-7/ADR cells was significantly reversed via the interaction between polymer and Pgp. Therefore, this type of polymer has potential superiority for cancer therapy.
基于以β-环糊精为中心的星形两亲性聚合物（sPEL/CD）的新型胶束系统可以实现阿霉素的递送。本研究特别探讨了 sPEL/CD 中聚乳酸段对各种胶束性质的影响，如临界胶束浓度、粒径、载药量、细胞毒性和耐药性逆转作用。
采用臂首法合成 sPEL/CD。采用芘作为探针，荧光分光光度法测定聚合物胶束的临界胶束浓度。采用油/水法制备阿霉素载药胶束。采用噻唑蓝（MTT）比色法、激光共聚焦显微镜和流式细胞术检测阿霉素载药胶束的细胞毒性和细胞摄取。最后，用罗丹明 123 摄取法评价聚合物对 MCF-7 和 MCF-7/ADR 细胞的作用。
所有聚合物均表现出低细胞毒性，其胶束具有理想的 pH 加速释放（pH5.0），有利于细胞质内药物传递。在聚合物中引入聚乳酸后，胶束的临界胶束浓度可有效降低，载药量增加。最重要的是，聚合物与 Pgp 相互作用可显著逆转 MCF-7/ADR 细胞的耐药性。因此，这类聚合物在癌症治疗方面具有潜在优势。
