The National Hepatobiliary & Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Pharmaceutical Sciences - Drug Development Division, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
Department of Pharmaceutical Sciences - Drug Development Division, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA.
Int J Pharm. 2012 Apr 15;426(1-2):193-201. doi: 10.1016/j.ijpharm.2012.01.020. Epub 2012 Jan 17.
Co-encapsulated doxorubicin (DOX) and curcumin (CUR) in poly(butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared with emulsion polymerization and interfacial polymerization. The mean particle size and mean zeta potential of CUR-DOX-PBCA-NPs were 133 ± 5.34 nm in diameter and +32.23 ± 4.56 mV, respectively. The entrapment efficiencies of doxorubicin and curcumin were 49.98 ± 3.32% and 94.52 ± 3.14%, respectively. Anticancer activities and reversal efficacy of the formulations and various combination approaches were assessed using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide assay and western blotting. The results showed that the dual-agent loaded PBCA-NPs system had the similar cytotoxicity to co-administration of two single-agent loaded PBCA-NPs (DOX-PBCA-NPs+CUR-PBCA-NPs), which was slightly higher than that of the free drug combination (DOX+CUR) and one free drug/another agent loaded PBCA-NPs combination (DOX+CUR-PBCA-NPs or CUR+DOX-PBCA-NPs). The simultaneous administration of doxorubicin and curcumin achieved the highest reversal efficacy and down-regulation of P-glycoprotein in MCF-7/ADR cell lines, an MCF-7 breast carcer cell line resistant to adriamycin. Multidrug resistance can be enhanced by combination delivery of encapsulated cytotoxic drugs and reversal agents.
载多柔比星（DOX）和姜黄素（CUR）的聚氰基丙烯酸正丁酯纳米粒（PBCA-NPs）通过乳液聚合和界面聚合来制备。CUR-DOX-PBCA-NPs 的平均粒径和平均 Zeta 电位分别为 133 ± 5.34nm 和 +32.23 ± 4.56mV。多柔比星和姜黄素的包封效率分别为 49.98 ± 3.32%和 94.52 ± 3.14%。采用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐法和 Western blot 法评估制剂和各种组合方法的抗癌活性和逆转效果。结果表明，载双药的 PBCA-NPs 系统与两种单药载 PBCA-NPs（DOX-PBCA-NPs+CUR-PBCA-NPs）的联合用药具有相似的细胞毒性，略高于游离药物组合（DOX+CUR）和一种游离药物/另一种药物载 PBCA-NPs 联合用药（DOX+CUR-PBCA-NPs 或 CUR+DOX-PBCA-NPs）。多柔比星和姜黄素同时给药在 MCF-7/ADR 细胞系（对阿霉素耐药的 MCF-7 乳腺癌细胞系）中实现了最高的逆转效果和 P-糖蛋白的下调，多药耐药性可以通过包裹细胞毒性药物和逆转剂的联合递送来增强。
