Cancer Nanomedicine Laboratory, Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
Int J Pharm. 2011 Oct 31;419(1-2):281-6. doi: 10.1016/j.ijpharm.2011.07.033. Epub 2011 Jul 27.
The aim of this study was to develop micellar nanocarriers for concomitant delivery of paclitaxel and 17-allylamino-17-demethoxygeldanamycin (17-AAG) for cancer therapy. Paclitaxel and 17-AAG were simultaneously loaded into polymeric micelles by a solvent evaporation method. Two candidate nanocarrier constructs, polyethylene glycol-poly(D, L-lactic acid) (PEG-PLA) micelles and PEG-distearoylphosphatidylethanolamine/tocopheryl polyethylene glycol 1000 (PEG-DSPE/TPGS) mixed micelles, were assessed for the release kinetics of the loaded drugs. Compared to PEG-PLA micelles, entrapment of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles resulted in significantly prolonged release half-lives. The simultaneous incorporation of paclitaxel and 17-AAG into PEG-DSPE/TPGS mixed micelles was confirmed by (1)H NMR analysis. Paclitaxel/17-AAG-loaded PEG-DSPE/TPGS mixed micelles were as effective in blocking the proliferation of human ovarian cancer SKOV-3 cells as the combined free drugs. PEG-DSPE/TPGS mixed micelles may provide a novel and advantageous delivery approach for paclitaxel/17-AAG combination therapy.
本研究旨在开发胶束纳米载体，用于同时递送紫杉醇和 17-烯丙基-17-去甲氧基格尔德霉素（17-AAG）用于癌症治疗。紫杉醇和 17-AAG 通过溶剂蒸发法同时载入聚合物胶束中。两种候选纳米载体构建体，聚乙二醇-聚（D，L-乳酸）（PEG-PLA）胶束和聚乙二醇二硬脂酰基磷脂酰乙醇胺/生育酚聚乙二醇 1000（PEG-DSPE/TPGS）混合胶束，用于评估载药的释放动力学。与 PEG-PLA 胶束相比，紫杉醇和 17-AAG 包封入 PEG-DSPE/TPGS 混合胶束中导致释放半衰期显著延长。通过（1）H NMR 分析证实了紫杉醇和 17-AAG 同时掺入 PEG-DSPE/TPGS 混合胶束中。紫杉醇/17-AAG 负载的 PEG-DSPE/TPGS 混合胶束在阻断人卵巢癌 SKOV-3 细胞增殖方面与联合游离药物一样有效。PEG-DSPE/TPGS 混合胶束可能为紫杉醇/17-AAG 联合治疗提供一种新颖有利的递药途径。
