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Edaravone, a cytoprotective drug, enhances transgene expression mediated by lipoplexes in HepG2 cells and mice


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タイトル: Edaravone, a cytoprotective drug, enhances transgene expression mediated by lipoplexes in HepG2 cells and mice
著者: Wang, Shu / Fumoto, Shintaro / Miyamoto, Hirotaka / Tanaka, Masakazu / Nishida, Koyo
発行日: 2018年 8月 5日
出版者: Elsevier B.V.
引用: International Journal of Pharmaceutics, 548(1), pp.173-181; 2018
抄録: A requirement of gene therapy is efficient nucleic acid delivery. However, the application of cationic liposomes to gene therapy is restricted by their inefficient transfection capacity, which may be caused by cytotoxicity. This cytotoxicity is highly dependent on cationic lipid-induced reactive oxygen species (ROS). Here, to provide cellular protection, we used edaravone, an efficacious anti-oxidative drug, to scavenge ROS during transfection using cationic liposome/plasmid DNA complexes (lipoplexes). Both free edaravone and edaravone-loaded liposomes (EDLPs) enhanced transgene expression in the human hepatoma cell line, HepG2, while EDLPs decreased the effective dose of edaravone. The cellular protective effect of edaravone was found to decrease the cytotoxicity of cationic liposomes. Edaravone was also effective in the commercial product, Lipofectamine® 3000, which may expand the application of edaravone to promote transfection efficiency. Compared with free edaravone, EDLPs also showed superior transgene expression in mice. Our findings will promote the development of efficient and safe gene therapy.
キーワード: Cationic liposomes / Cytoprotection / Edaravone / Non-viral vector / Reactive oxygen species / Transfection
URI: http://hdl.handle.net/10069/38520
ISSN: 03785173
DOI: 10.1016/j.ijpharm.2018.06.068
権利: © 2018 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
資料タイプ: Journal Article
原稿種類: author
出現コレクション:050 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38520

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