高容量聚（2-恶唑啉）胶束中多种化疗药物的协同组合
Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles.
作者信息
Han Yingchao, He Zhijian, Schulz Anita, Bronich Tatiana K, Jordan Rainer, Luxenhofer Robert, Kabanov Alexander V
机构信息
Center for Drug Delivery and Nanomedicine and Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5830, United States.
出版信息
Mol Pharm. 2012 Aug 6;9(8):2302-13. doi: 10.1021/mp300159u. Epub 2012 Jun 28.
Abstract
Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.
摘要
许多用于癌症治疗的有效药物水溶性较差。在联合化疗中，添加剂配方中所需的辅料往往具有毒性，限制了它们在临床干预中的应用。在此，我们报道了两亲性聚（2-恶唑啉）（POx）胶束作为一种有前景的高容量多药癌症化疗递送平台。紫杉醇（PTX）、多西他赛（DTX）、17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）、依托泊苷（ETO）和硼替佐米（BTZ）的多种二元和三元药物组合被溶解在特定的聚合物胶束中，最终制剂中药物的总负载量达到了前所未有的高达50 wt%，实现了高容量负载。与单药负载的胶束相比，多药负载的POx胶束表现出更高的稳定性。在MCF-7癌细胞中观察到胶束ETO/17-AAG的药物比例依赖性协同细胞毒性，在MCF-7、PC3、MDA-MB-231和HepG2细胞中观察到胶束BTZ/17-AAG的药物比例依赖性协同细胞毒性。
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