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纳米载体系统将奥沙利铂选择性递送至肿瘤组织可增强包封的奥沙利铂的整体治疗效果。

Selective delivery of oxaliplatin to tumor tissue by nanocarrier system enhances overall therapeutic efficacy of the encapsulated oxaliplatin.

作者信息

Lila Amr Selim Abu, Kiwada Hiroshi, Ishida Tatsuhiro

机构信息

Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima.

出版信息

Biol Pharm Bull. 2014;37(2):206-11. doi: 10.1248/bpb.b13-00540.

Abstract

Oxaliplatin (trans-l-diaminocyclohexane oxalatoplatinum; l-OHP), a third-generation platinum antitumor drug, is currently approved in combination with 5-flurouracil (5-FU)/leucovorin (FOLFOX) for standard first- and second-line treatment of metastatic or advanced-stage colorectal cancer. Despite l-OHP's better tolerability in comparison with other platinum compounds such as cisplatin and carboplatin, its clinical efficiency is limited by the dose-limiting side effects including cumulative neurotoxicity and acute dysesthesias. In addition, like other platinum chemotherapeutic agents, l-OHP therapy is limited by reduced accumulation levels in tumor tissues, nonselective accumulation in healthy organs and/or tissues, inactivation by conjugation with glutathione, and the development of drug resistance. Accordingly, successful outcome of cancer treatment using l-OHP requires selective delivery of a relatively high concentration of the drug to tumor tissues. In this review we focus on utilization of different drug-delivery vehicles such as liposomes, polymeric nanocarriers, and carbon nanotubes in enhancing selective delivery of l-OHP to tumor tissues and consequently improving overall efficacy of l-OHP-containing drug-delivery systems.

摘要

奥沙利铂(反式-1,2-二氨基环己烷草酸铂;l-OHP)是一种第三代铂类抗肿瘤药物,目前已被批准与5-氟尿嘧啶(5-FU)/亚叶酸钙(FOLFOX)联合用于转移性或晚期结直肠癌的标准一线和二线治疗。尽管与顺铂和卡铂等其他铂类化合物相比,l-OHP的耐受性更好,但其临床疗效受到剂量限制性副作用的限制,包括累积性神经毒性和急性感觉异常。此外,与其他铂类化疗药物一样,l-OHP治疗受到肿瘤组织中蓄积水平降低、在健康器官和/或组织中非选择性蓄积、与谷胱甘肽结合而失活以及耐药性发展的限制。因此,使用l-OHP成功治疗癌症需要将相对高浓度的药物选择性地递送至肿瘤组织。在本综述中,我们重点关注脂质体、聚合物纳米载体和碳纳米管等不同药物递送载体在增强l-OHP向肿瘤组织的选择性递送以及从而提高含l-OHP药物递送系统的整体疗效方面的应用。

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