Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models
Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models
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DOI：
10.1215/15228517-2008-068
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发表时间：
2009-04-01
期刊：
影响因子：
15.9
通讯作者：
Tominaga, Teiji
中科院分区：
文献类型：
--
作者：
Inoue, Tomoo;Yamashita, Yoji;Tominaga, Teiji
近年来，对流增强给药系统作为一种新型的化疗药物治疗方法，克服了目前脑肿瘤化疗中存在的问题。聚合物胶束系统在全身给药中表现出显著更高的体内抗肿瘤活性。本研究在9 L同系大鼠模型中研究了聚合胶束阿霉素（DOX）CED的有效性。评价了CED输注的游离、脂质体和胶束DOX的分布、毒性和疗效。与游离DOX相比，胶束DOX在脑肿瘤组织和周围正常脑组织中的分布更广。组织毒性在较高剂量下增加，但用胶束DOX处理的大鼠在任何测试剂量（0.1-1.0 mg/ml）下均未显示异常神经症状。与相同剂量（0.2mg/ml）的游离DOX（19.6天; p = 0.0173）和脂质体DOX（16.6天; p = 0.0007）相比，通过CED输注的胶束DOX导致延长的中位存活期（36天）。本研究表明，CED与聚合物胶束药物载体系统用于治疗脑肿瘤的潜力。Neuro-Oncology 11，151-157，2009（发布到Neuro-Oncology [serial online]，Doc. D 08 -00039，2008年8月28日。网址http://neuro-oncology.dukejournals.org; DOI：10.1215/15228517-2008-068）
Convection-enhanced delivery (CED) with various drug carrier systems has recently emerged as a novel chemotherapeutic method to overcome the problems of current chemotherapies against brain tumors. Polymeric micelle systems have exhibited dramatically higher in vivo antitumor activity in systemic administration. This study investigated the effectiveness of CED with polymeric micellar doxorubicin (DOX) in a 9L syngeneic rat model. Distribution, toxicity, and efficacy of free, liposomal, and micellar DOX infused by CED were evaluated. Micellar DOX achieved much wider distribution in brain tumor tissue and surrounding normal brain tissue than free DOX. Tissue toxicity increased at higher doses, but rats treated with micellar DOX showed no abnormal neurological symptoms at any dose tested (0.1-1.0 mg/ml). Micellar DOX infused by CED resulted in prolonged median survival (36 days) compared with free DOX (19.6 days; p = 0.0173) and liposomal DOX (16.6 days; p = 0.0007) at the same dose (0.2 mg/ml). This study indicates the potential of CED with the polymeric micelle drug carrier system for the treatment of brain tumors. Neuro-Oncology 11, 151-157, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00039, August 28, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-068)