Delivery of pDNA to the Lung by Lipopolyplexes Using N-Lauroylsarcosine and Effect on the Pulmonary Fibrosis

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...

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Autores principales:	Tomoaki Kurosaki, Hiroki Kanda, Junya Hashizume, Kayoko Sato, Hitomi Harasawa, Tadahiro Nakamura, Hitoshi Sasaki, Yukinobu Kodama
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gene delivery shRNA nanoparticles pulmonary fibrosis <i>N</i>-lauroylsarcosine Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/0208892e048c44ed97c76acfa0360944
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spelling	oai:doaj.org-article:0208892e048c44ed97c76acfa03609442021-11-25T18:42:49ZDelivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis10.3390/pharmaceutics131119831999-4923https://doaj.org/article/0208892e048c44ed97c76acfa03609442021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1983https://doaj.org/toc/1999-4923In a previous study, we constructed a lung-targeting lipopolyplex containing polyethyleneimine (PEI), 1,2-di-<i>O</i>-octadecenyl-3-trimethylammonium propane (DOTMA), and <i>N</i>-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.Tomoaki KurosakiHiroki KandaJunya HashizumeKayoko SatoHitomi HarasawaTadahiro NakamuraHitoshi SasakiYukinobu KodamaMDPI AGarticlegene deliveryshRNAnanoparticlespulmonary fibrosis<i>N</i>-lauroylsarcosinePharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1983, p 1983 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gene delivery shRNA nanoparticles pulmonary fibrosis <i>N</i>-lauroylsarcosine Pharmacy and materia medica RS1-441
spellingShingle	gene delivery shRNA nanoparticles pulmonary fibrosis <i>N</i>-lauroylsarcosine Pharmacy and materia medica RS1-441 Tomoaki Kurosaki Hiroki Kanda Junya Hashizume Kayoko Sato Hitomi Harasawa Tadahiro Nakamura Hitoshi Sasaki Yukinobu Kodama Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
description	In a previous study, we constructed a lung-targeting lipopolyplex containing polyethyleneimine (PEI), 1,2-di-<i>O</i>-octadecenyl-3-trimethylammonium propane (DOTMA), and <i>N</i>-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.
format	article
author	Tomoaki Kurosaki Hiroki Kanda Junya Hashizume Kayoko Sato Hitomi Harasawa Tadahiro Nakamura Hitoshi Sasaki Yukinobu Kodama
author_facet	Tomoaki Kurosaki Hiroki Kanda Junya Hashizume Kayoko Sato Hitomi Harasawa Tadahiro Nakamura Hitoshi Sasaki Yukinobu Kodama
author_sort	Tomoaki Kurosaki
title	Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
title_short	Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
title_full	Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
title_fullStr	Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
title_full_unstemmed	Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis
title_sort	delivery of pdna to the lung by lipopolyplexes using <i>n</i>-lauroylsarcosine and effect on the pulmonary fibrosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0208892e048c44ed97c76acfa0360944
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Delivery of pDNA to the Lung by Lipopolyplexes Using <i>N</i>-Lauroylsarcosine and Effect on the Pulmonary Fibrosis

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