Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors  

作　　者：Xiong Guo Zhiyue Zhao Dawei Chen Mingxi Qiao Feng Wan Dongmei Cun Yi Sun Mingshi Yang 

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Wenhua Road No.103,Shenyang 110016,China [2]School of Graduate,Liaoning University of Traditional Chinese Medicine,Chong Shan Road No.79,Shenyang 110847,China [3]School of Pharmacy,Shenyang Pharmaceutical University,Wenhua Road No.103,Shenyang 110016,China [4]Department of Pharmacy,Faculty of Health and Medical Sciences,University of Copenhagen,Universitetsparken 2,DK-2100 Copenhagen O,Denmark [5]Department of Micro-and Nanotechnology,Technical University of Denmark,φsteds Plads,Kgs.Lyngby 2800,Denmark

出　　处：《Asian Journal of Pharmaceutical Sciences》2019年第1期78-85,共8页亚洲药物制剂科学（英文）

基　　金：the Liaoning Province Pan Deng Xue Zhe Grant(M.Yang);Liaoning Provincial Education officer’s Excellent Talents Supporting Plan(D.Cun);National Natural Science Foundation of China(No.81302720 and 81573380)for financial support。

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.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/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.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.

关 键 词：RESVERATROL DOCETAXEL Methoxyl poly(ethylene glycol)-poly(d l-lactide)copolymer (mPEG-PDLA) Micelles Drug resistance tumor 

分 类 号：R283.6[医药卫生—中药学]