Enhanced efficiency of thermally targeted taxanes delivery in a human xenograft model of gastric cancer
Enhanced efficiency of thermally targeted taxanes delivery in a human xenograft model of gastric cancer
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提高人类胃癌异种移植模型中热靶向紫杉烷递送的效率
DOI：
10.1002/jps.21194
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发表时间：
2008-08-01
影响因子：
3.8
通讯作者：
Yu, Lixia
中科院分区：
文献类型：
--
作者：
Liu, Baorui;Yang, Mi;Yu, Lixia
由于成功的紫杉烷类化疗需要改善其治疗指数，特别是通过减少不必要的全身毒性的药物或佐剂，我们已经调查，并正在报告的结果，从使用一种新的聚合物热敏胶束递送系统的多西他赛和紫杉醇的调查。本文报道了一种新型亚稳态温敏聚合物胶束[poly（N-异丙基丙烯酰胺-co-丙烯酰胺）-b-poly（DL-丙交酯），Poly（IPAAm-co-AAm）-b-PDLLA]，用于多西他赛和紫杉醇的缓释。先前的体外疗效研究表明，在高温下，紫杉醇负载胶束对不同的肿瘤细胞系显示出比常规多西他赛制剂更强的细胞毒性，而对正常细胞显示出较轻的毒性。目前的体内研究表明，在相同剂量水平的多西他赛（紫杉醇），热疗大大增强了胶束多西他赛（紫杉醇）在人胃BGC小鼠异种移植模型中的抗肿瘤作用，显示出超过80%的非凡的肿瘤体积和重量生长抑制百分比。同时，急性毒性试验显示，与对照组相比，高温和多西他赛胶束（紫杉醇）联合用药的LD 50较低。本研究结果表明，聚（IPAAm-co-AAm）-b-PDLLA胶束可能是一种临床有用的化疗制剂，值得进一步研究，以评估临床应用的可行性。(C)2007 Wiley-Liss，Inc.和美国药剂师协会
Since successful chemotherapy with taxanes requires an improvement in their therapeutic index, especially by the reduction in unwanted systemic toxicity of either drug or adjuvants, we have investigated and are reporting results from an investigation of the use of a novel polymeric thermosensitive micellar delivery system for docetaxel and paclitaxel. Here we reported a novel metastable thermosensitive polymeric micelle for docetaxel and paclitaxel delivery [poly(N-isopropylacrylamide-co-acrylamide)-b-poly(DL-lactide), Poly(IPAAm-co-AAm)-b-PDLLA]. Previous in vitro efficacy studies indicated that, with hyperthermia, docetaxel-loaded micelles showed stronger cytotoxicity to different tumor cell lines than conventional docetaxel formulation while exhibiting slighter toxicity to normal cells. Present in vivo studies indicated that at the same dose level of docetaxel (paclitaxel), hyperthermia greatly enhanced the antitumor effect of micellar docetaxel (paclitaxel) in human gastric BGC mouse xenograft model by showing an extraordinary tumor volume and weight growth percentage inhibition of more than 80%. Meanwhile, acute toxicity tests features the lower LD50 Of the combination of hyperthermia and micellar docetaxel (paclitaxel) compared to that of the control group. The present results suggest that poly(IPAAm-co-AAm)-b-PDLLA micelles could be a clinically useful chemotherapeutic formulation and merit further research to evaluate the feasibility of clinical application. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.