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《Asian Journal of Pharmaceutical Sciences》 2019年01期
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Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Xiong Guo  Zhiyue Zhao  Dawei Chen  Mingxi Qiao  Feng Wan  Dongmei Cun  Yi Sun  Mingshi Yang  
【摘要】:Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX) via polymeric nanocarriers to treat breast cancer. To this end, methoxyl poly(ethylene glycol)-poly(D,L-lactide) copolymer(mPEG-PDLA) was prepared and characterized using FTIR and ~1H NMR, and their molecular weights were determined by GPC. Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells). Subsequently, RES and DTX were loaded in the mPEG-PDLA micelles simultaneously, and the morphology, particle size distribution, in vitro release, pharmacokinetic profiles, as well as cytotoxicity to the MCF-7 cells were characterized. IC_(50) of RES and DTX in MCF-7 cells were determined to be 23.0 μg/ml and 10.4 μg/ml, respectively, while a lower IC_(50) of 4.8 μg/ml of the combination of RES and DTX was obtained. The combination of RES and DTX at a ratio of 1:1(w/w) generated stronger synergistic effect than other ratios in the MCF-7 cells. RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles, and enhanced cytotoxicity in vitro against MCF-7 cells. The AUC_(( 0→t)) of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs. These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

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