Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors
Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors
复制标题
通过聚合物胶束共同递送白藜芦醇和多西紫杉醇以改善耐药肿瘤的治疗
DOI：
10.1016/j.ajps.2018.03.002
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发表时间：
2019-01-01
影响因子：
10.2
通讯作者：
Yang, Mingshi
中科院分区：
文献类型：
--
作者：
Guo, Xiong;Zhao, Zhiyue;Yang, Mingshi
抗癌药物联合给药有望提高癌症治疗效果。本研究旨在探讨通过聚合物纳米载体同时给药白藜芦醇(RES)和多西紫杉醇(DTX)治疗乳腺癌的可能性。为此，合成了甲氧基聚乙二醇-聚(D，L-丙交酯)共聚物，并用傅立叶变换红外光谱和核磁共振氢谱对其结构进行了表征，用凝胶渗透色谱仪测定了其相对分子质量。通过等速曲线分析和组合指数计算，找出RES和DTX对人乳腺癌细胞株(MCF-7细胞)的最佳比例。随后，将RES和DTX同时负载到mGFP-PDLA胶束中，并对其形态、粒径分布、体外释放、药代动力学以及对MCF-7细胞的细胞毒性进行了表征。白藜芦醇和DTX对MCF-7细胞的IC50分别为23.0mU/ml和10.4mU/ml，而白藜芦醇和DTX合用的IC50为4.8mU/ml。白藜芦醇和DTX以1：1(w/w)的比例联合使用时，在MCF-7细胞中产生的协同作用比其他比例更强。RES和DTX负载的mpeg-PDLA胶束具有较长的释药曲线，并增强了体外对MCF-7细胞的细胞毒作用。静注后DTX和RES在mpeg-PDLA胶束中的AUC((0-gt；t))。大鼠给药分别是静脉注射的3.0倍和1.6倍。个别药物的注射。这些结果表明，使用mpeg-PDLA胶束共传递RES和DTX可以更好地治疗肿瘤。(三)2018沈阳药科大学。由Elsevier B.V.出版。这是一篇CC BY-NC-ND许可证下的开放获取文章。(http://creativecommons.org/licenses/by-nc-nd/4.0/)
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 H-1 NMR, and their molecular weights were determined by GPC. Isobolo-gram 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 mu g/ml and 10.4 mu g/ml, respectively, while a lower IC50 of 4.8 mu g/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. (c) 2018 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)