Lila Amr Selim Abu, Kiwada Hiroshi, Ishida Tatsuhiro
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima.
Biol Pharm Bull. 2014;37(2):206-11. doi: 10.1248/bpb.b13-00540.
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.
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。