Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou.
Int J Nanomedicine. 2011;6:1955-62. doi: 10.2147/IJN.S23099. Epub 2011 Sep 12.
Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.
Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.
Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.
This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.
多药耐药仍然是癌症化疗成功的主要障碍。一些化学多药耐药抑制剂，如环孢菌素和维拉帕米，已被报道能逆转肿瘤细胞的耐药性。然而，伴随的副作用限制了它们的临床应用。在这项研究中，我们开发了一种新的药物传递系统，即聚乙二醇-聚己内酯（PEG-PCL）共聚物胶束包封阿霉素，以克服阿霉素耐药 K562 肿瘤细胞的耐药性。
制备了阿霉素负载的两亲性嵌段共聚物 PEG-PCL 胶束，并研究了这些胶束的理化性质、阿霉素在阿霉素耐药 K562 肿瘤细胞中的积累和细胞毒性。
采用溶剂蒸发法制备阿霉素载药胶束，粒径为 36nm，Zeta 电位为+13.8mV。阿霉素的包封率为 48.6%±2.3%。胶束表现出持续释放、增加摄取和细胞毒性，以及降低阿霉素在阿霉素耐药 K562 肿瘤细胞中的外排。
本研究表明，PEG-PCL 胶束有可能逆转肿瘤细胞的多药耐药性。
