Sequential administration with oxaliplatin-containing PEG-coated cationic liposomes promotes a significant delivery of subsequent dose into murine solid tumor

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.