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Delivery of pDNA to the Lung by Lipopolyplexes Using N-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
http://hdl.handle.net/10069/00041195
http://hdl.handle.net/10069/0004119591ca6257-ae14-4641-a1e7-4a858747afac
名前 / ファイル | ライセンス | アクション |
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Pharmaceutics13_1983.pdf (1.9 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-01-28 | |||||
タイトル | ||||||
タイトル | Delivery of pDNA to the Lung by Lipopolyplexes Using N-Lauroylsarcosine and Effect on the Pulmonary Fibrosis | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | gene delivery | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | shRNA | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | nanoparticles | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | pulmonary fibrosis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | N-lauroylsarcosine | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kurosaki, Tomoaki
× Kurosaki, Tomoaki× Kanda, Hiroki× Hashizume, Junya× Sato, Kayoko× Harasawa, Hitomi× Nakamura, Tadahiro× Sasaki, Hitoshi× Kodama, Yukinobu |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In a previous study, we constructed a lung-targeting lipopolyplex containing polyethyleneimine (PEI), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), and N-lauroylsarcosine (LS). The lipopolyplex exhibited an extremely high gene expression in the lung after intravenous administration. Here, we optimized the lipopolyplex and used it to deliver a TGF-β1 shRNA to treat refractory pulmonary fibrosis. We constructed several lipopolyplexes with pDNA, various cationic polymers, cationic lipids, and LS to select the most effective formulation. Then, the pDNA encoding shRNA against mouse TGF-β1 was encapsulated in the lipopolyplex and injected into mice with bleomycin-induced pulmonary fibrosis. After optimizing the lipopolyplex, dendrigraft poly-L-lysine (DGL) and DOTMA were selected as the appropriate cationic polymer and lipid, respectively. The lipopolyplex was constructed with a pDNA, DGL, DOTMA, and LS charge ratio of 1:2:2:4 showed the highest gene expression. After intravenous administration of the lipopolyplex, the highest gene expression was observed in the lung. In the in vitro experiment, the lipopolyplex delivered pDNA into the cells via endocytosis. As a result, the lipopolyplex containing pDNA encoding TGF-β1 shRNA significantly decreased hydroxyproline in the pulmonary fibrosis model mice. We have successfully inhibited pulmonary fibrosis using a novel lung-targeting lipopolyplex. | |||||
書誌情報 |
Pharmaceutics 巻 13, 号 11, p. 1983, 発行日 2021-11-22 |
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出版者 | ||||||
出版者 | MDPI | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1999-4923 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/pharmaceutics13111983 | |||||
権利 | ||||||
権利情報 | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Pharmaceutics, 13(11), art. no. 1983; 2021 |