Sequential administration with oxaliplatin-containing PEG-coated cationic liposomes promotes a significant delivery of subsequent dose into murine solid tumor
Sequential administration with oxaliplatin-containing PEG-coated cationic liposomes promotes a significant delivery of subsequent dose into murine solid tumor
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DOI：
10.1016/j.jconrel.2009.10.020
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发表时间：
2010-03-03
影响因子：
10.8
通讯作者：
Kiwada, Hiroshi
中科院分区：
文献类型：
--
作者：
Abu Lila, Amr S.;Doi, Yusuke;Kiwada, Hiroshi
最近，我们设计了一种PEG包被的阳离子脂质体，以实现I-OHP在实体瘤中的肿瘤内皮细胞和肿瘤细胞的双重靶向递送。靶向脂质体I-OHP制剂在小鼠肿瘤模型中连续注射三次脂质体I-OHIP后显示出有效的抗肿瘤活性。这使我们假设先前给药脂质体可能会增强后续剂量的肿瘤内蓄积，从而提高截留的I-OHP的治疗功效。本研究表明，虽然一个单一的脂质体I-OHP注射并没有增强随后的测试PEG包被的阳离子脂质体的肿瘤积累，脂质体I-OHP的两个连续注射。由PEG包被的阳离子脂质体递送的I-OHP的累积细胞毒性效应导致后续剂量的脂质体I-OHP在实体瘤中深度扩散，这可能是由于肿瘤内间隙扩大的结果。我们的研究表明，序贯注射靶向脂质体抗癌药物在增强向难治性实体瘤中递送足量抗癌药物方面具有重要的临床和实践意义，从而可以实现显著的抗癌疗效。(C)2009 Elsevier B. V.保留所有权利。
Recently, we designed a PEG-coated cationic liposome to achieve dual targeting delivery of I-OHP to both tumor endothelial cells and tumor cells in a solid tumor. The targeted liposomal I-OHP formulation showed an efficient antitumor activity in a murine tumor model after three sequential liposomal I-OHIP injections. This led us to assume that prior dosing with liposomes might enhance the intra-tumoral accumulation of a subsequent dose, and hence improve the therapeutic efficacy of entrapped I-OHP. The present study shows that while a single liposomal I-OHP injection does not enhance tumor accumulation of subsequent test-PEG-coated cationic liposomes, two sequential injections of liposomal I-OHP do. Cumulative cytotoxic effects of I-OHP delivered by PEG-coated cationic liposomes led to deep diffusion of a subsequent dose of liposomal I-OHP in solid tumor presumably as a result of the enlarged intra-tumoral interstitial space. Our study suggests that sequential injections of a targeted liposonnal anticancer drug is of significant clinical and practical importance in enhancing the delivery of adequate quantities of anticancer agents into intractable solid tumors, and thereby may achieve a significant anticancer efficacy. (C) 2009 Elsevier B.V. All rights reserved.