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*

*Corresponding author for this work

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Abstract

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. Isobolgram 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 23.0 μg/ml and 10.4 μg/ml, respectively, while a lower IC50 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.
Original languageEnglish
JournalAsian Journal of Pharmaceutical Sciences
Volume14
Issue number1
Pages (from-to)78-85
ISSN1818-0876
DOIs
Publication statusPublished - 2019

Keywords

  • Resveratrol
  • Docetaxel
  • Methoxyl poly(ethylene glycol)-poly( d,l -lactide) copolymer
  • (mPEG-PDLA)
  • Micelles
  • Drug resistance tumor

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