阿霉素-姜黄素聚氰基丙烯酸正丁酯复方纳米粒的研制及逆转MCF-7/ADR细胞多药耐药的研究

Study of Co-encapsulated Doxorubicin and Curcumin Poly(butyl cyanoacrylate) Nanoparticles and Reversion of Multidrug Resistance in MCF/ADR Cell Line

采用乳化聚合法制备阿霉素-姜黄素聚氰基丙烯酸正丁酯复方纳米粒(DOX-CUR-PBCA-NPs),该纳米粒平均粒径为133±5.34nm,Zeta电位为+32.23±4.56 mV,阿霉素(DOX)和姜黄素(CUR)的包封率分别为49.98±3.32%,94.52±3.14%。MTT实验结果和Western blott实验结果均表明,DOX-CUR-PBCA-NPs与CUR-PBCA-NPs+DOX-PBCA-NPs体外对MCF-7/ADR细胞的生长抑制活性相当,下调MCF-7/ADR细胞中P-糖蛋白(P-gp)的表达也相当,较没有用PBCA纳米粒包载的游离药物、单一药物的纳米制剂及其他形式的制剂联用的抗肿瘤活性及逆转多药耐药的性能都显著增强。说明利用PBCA纳米粒同时包裹抗癌药物阿霉素与中药逆转剂姜黄素协同用药可以增强克服多药耐药(MDR)的疗效。

Co-encapsulated doxornbicin and curcumin in PBCA nanoparticles were prepared with emulsion polymerization. The mean particle size and the zeta potential of DOX-CUR-PBCA-NPs were 133 ± 5.34nm in diameter and ＋ 32.23 _± 4.56 mV, respectively. The entrapment efficiencies of DOX and CUR 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 MTF 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 DOX and CUR could achieve the highest reversal efficacy, and down-regulate of P-gp in MCF-7/ADR cell lines. Muhidrug-resistant can be enhanced by treated combination of encapsulated cytotoxic drugs and reversal agents. Co-encapsulation of anticaneer drug DOX and reversal agent CUR can be more effective in reversing multi-drug resistance than the other formulations and might cause lower normal tissue drug toxicity and fewer drug-drug interactions.