Tang Jingling, Ji Hongyu, Ren Jinmei, Li Mengting, Zheng Nannan, Wu Linhua
Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Key Laboratory of Medications Research, College of Heilongjiang Province, Harbin, Heilongjiang 150086, P.R. China.
Oncol Lett. 2017 Jan;13(1):389-395. doi: 10.3892/ol.2016.5421. Epub 2016 Nov 23.
Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs]. TPGS and Brij 78 could sensitize MDR tumors by inhibiting the P-gp drug efflux system. The combination of Cur and Pip, when administered in SLNs formulations, resulted in a significant enhancement in cytotoxicity and allowed efficient intracellular delivery of the drugs in drug-resistant A2780/Taxol cells. This dual inhibitory strategy may have significant potential in the clinical management of MDR in cancer.
多药耐药性（MDR）是癌症化疗的主要临床障碍，而P-糖蛋白（P-gp）的过表达是一个关键因素。在本研究中，设计并开发了一种用于逆转多药耐药性的新型共递送系统。该系统由包裹在固体脂质纳米粒（SLNs）中的姜黄素（Cur）和胡椒碱（Pip）组成，并添加了聚乙二醇琥珀酸生育酚酯（TPGS）和月桂醇聚醚-78 [（Cur+Pip）-SLNs]。TPGS和月桂醇聚醚-78可通过抑制P-gp药物外排系统使多药耐药肿瘤敏感化。当以SLNs制剂形式给药时，Cur和Pip的组合可显著增强细胞毒性，并使药物在耐药A2780/紫杉醇细胞中实现高效的细胞内递送。这种双重抑制策略在癌症多药耐药性的临床管理中可能具有巨大潜力。
