Improved intratumoral delivery of PEG-coated siRNA-lipoplexes by combination with metronomic S-1 dosing in a murine solid tumor model

Drug Delivery and Translational Research
Tatsuaki TagamiHiroshi Kiwada

Abstract

Efficient systemic siRNA delivery to cells in the target tissue is a current critical challenge in the drug delivery field. Several studies have demonstrated that nanoparticles such as polyethylene glycol (PEG)-coated siRNA-lipoplexes may enhance the systemic delivery of siRNA to tumor. However, the disordered tumor microenvironment still poses a potential impediment with respect to the efficient delivery of PEG-coated siRNA-lipoplexes. Recently, we showed that metronomic S-1 dosing (daily oral administration) enhanced the accumulation of PEG-coated siBcl-2-lipoplex in DLD-1 solid tumor mouse model. In this study, to extend our work, we investigated the effect of metronomic S-1 dosing on the intratumoral accumulation and, thereby, therapeutic efficacy of PEG-coated siAgo2-lipoplex in Lewis lung carcinoma cells (LLCC) solid tumor mouse model. Also, we tried to elucidate the probable mechanism of the enhanced intratumoral accumulation of PEG-coated siRNA-lipoplexes induced by S-1 combination therapy. Results showed that metronomic S-1 dosing improved systemic delivery of intravenously injected PEG-coated siAgo2-lipoplexes into a LLCC solid tumor. In addition, the combined therapy of S-1 and PEG-coated siRNA-lipoplexes resulted in...Continue Reading

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Citations

Nov 4, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuvraj SinghManish K Chourasia
Nov 14, 2016·Cancer Letters·Amr S Abu Lila, Tatsuhiro Ishida
Mar 2, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tatsuhiro Ishida, Hiroshi Kiwada

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