The antitumor effect of novel docetaxel-loaded thermosensitive micelles
The antitumor effect of novel docetaxel-loaded thermosensitive micelles
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新型多西他赛热敏胶束的抗肿瘤作用
DOI：
10.1016/j.ejpb.2008.01.015
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发表时间：
2008-06-01
影响因子：
4.9
通讯作者：
Jiang, Xiqun
中科院分区：
文献类型：
--
作者：
Liu, Baorui;Yang, Mi;Jiang, Xiqun
为了进一步评价我们之前合成的基于生物可降解热敏共聚物poly（n -异丙基丙烯酰胺-co-丙烯酰胺）-b-poly（DL-lactide）的新型多西他赛负载胶束，本文采用不同肿瘤细胞系，采用标准MTT法研究了其对三种不同肿瘤细胞系的体外细胞毒性，并在昆明小鼠中进行了急性毒性研究和肿瘤分布研究。同时对C57BL/6小鼠进行体内抗肿瘤作用和毒性评价。根据我们的研究结果，负载多西他赛胶束的体外细胞毒性在37℃时低于常规多西他赛配方，而热疗大大增强了负载药物胶束的功效。急性毒性研究表明，与传统的多西他赛配方相比，负载多西他赛胶束的毒性降低。此外，多西他赛负载胶束使得肿瘤中的多西他赛浓度明显高于传统的多西他赛配方。此外，多西他赛负载胶束伴热疗的小鼠抗肿瘤效果显著提高；装载多西他赛的胶束也能减轻小鼠的体重。本研究表明，新型负载多西他赛的胶束具有增强的抗肿瘤功效和降低毒性的作用，并显示了其临床应用前景。(c) 2008 Elsevier B.V.版权所有
To further evaluate the novel docetaxel-loaded micelle based on the biodegradable thermosensitive copolymer poly(N-isopropylacrylamide-co-acrylamide)-b-poly(DL-lactide) that we had synthesized before, in this paper, we studied its in vitro cytotoxicity in three different tumor cell lines by standard MTT assays using different tumor cell lines, followed by studies of acute toxicity and the tumor distribution studies which were conducted in Kunming mice. Meanwhile, the in vivo antitumor efficacy as well as toxicity of the micelle was evaluated in C57BL/6 mice. According to our findings, the in vitro cytotoxicity of docetaxel-loaded micelles was lower than that of the conventional docetaxel formulation at 37 degrees C, while hyperthermia greatly enhanced the efficacy of drug-loaded micelles. The acute toxicity study showed reduced toxicity of docetaxel-loaded micelle compared to that of conventional docetaxel formulation. Moreover, docetaxel-loaded micelle enabled a prominent higher docetaxel concentration in tumor than conventional docetaxel formulation. Furthermore, a significantly higher antitumor efficacy was observed in mice treated with docetaxel-loaded micelles accompanied by hyperthermia; docetaxel-loaded micelles also caused less body weight loss of mice. This study demonstrates an increased antitumor efficacy and reduced toxicity of the novel docetaxel-loaded micelle and indicates its prospect of clinical applications. (c) 2008 Elsevier B.V. All rights reserved.