Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension

Abstract Clinical outcomes of pulmonary arterial hypertension (PAH) may be improved using targeted delivery system. We investigated the efficacy of ONO1301 (prostacyclin agonist) nanospheres (ONONS) in Sugen5416/hypoxia rat models of PAH. The rats were injected with saline (control) or ONONS (n = 10...

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Autores principales:	Tomomitsu Kanaya, Shigeru Miyagawa, Takuji Kawamura, Yoshiki Sakai, Kenta Masada, Nobutoshi Nawa, Hidekazu Ishida, Jun Narita, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0a7092285df41cc9b0a00ae9053c163
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spelling	oai:doaj.org-article:a0a7092285df41cc9b0a00ae9053c1632021-12-02T13:26:32ZInnovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension10.1038/s41598-021-86781-32045-2322https://doaj.org/article/a0a7092285df41cc9b0a00ae9053c1632021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86781-3https://doaj.org/toc/2045-2322Abstract Clinical outcomes of pulmonary arterial hypertension (PAH) may be improved using targeted delivery system. We investigated the efficacy of ONO1301 (prostacyclin agonist) nanospheres (ONONS) in Sugen5416/hypoxia rat models of PAH. The rats were injected with saline (control) or ONONS (n = 10, each) on days 21 and 28, respectively. Hepatocyte growth factor (HGF)-expressing fibroblasts and inflammatory cytokines were measured. Cardiac performance was assessed and targeted delivery was monitored in vivo, using Texas red-labeled nanoparticles. Compared with control, HGF-expressing fibroblasts and HGF expression levels were significantly higher in the ONONS group, while the levels of interleukin-6, interleukin-1β, transforming growth factor-β, and platelet-derived growth factor were lower. Histological assessment revealed significant amelioration of the percent medial wall thickness in pulmonary vasculature of rats in the ONONS group. Rats in the ONONS group showed decreased proliferating cell nuclear antigen-positive smooth muscle cells and improved right ventricle pressure/left ventricle pressure. No difference was seen in the accumulation of Texas red-labeled nanoparticles in the brain, heart, liver, and spleen between PAH and normal rats. However, a significant area of nanoparticles was detected in the lungs of PAH rats. ONONS effectively ameliorated PAH, with selective delivery to the damaged lung.Tomomitsu KanayaShigeru MiyagawaTakuji KawamuraYoshiki SakaiKenta MasadaNobutoshi NawaHidekazu IshidaJun NaritaKoichi TodaToru KurataniYoshiki SawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomomitsu Kanaya Shigeru Miyagawa Takuji Kawamura Yoshiki Sakai Kenta Masada Nobutoshi Nawa Hidekazu Ishida Jun Narita Koichi Toda Toru Kuratani Yoshiki Sawa Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
description	Abstract Clinical outcomes of pulmonary arterial hypertension (PAH) may be improved using targeted delivery system. We investigated the efficacy of ONO1301 (prostacyclin agonist) nanospheres (ONONS) in Sugen5416/hypoxia rat models of PAH. The rats were injected with saline (control) or ONONS (n = 10, each) on days 21 and 28, respectively. Hepatocyte growth factor (HGF)-expressing fibroblasts and inflammatory cytokines were measured. Cardiac performance was assessed and targeted delivery was monitored in vivo, using Texas red-labeled nanoparticles. Compared with control, HGF-expressing fibroblasts and HGF expression levels were significantly higher in the ONONS group, while the levels of interleukin-6, interleukin-1β, transforming growth factor-β, and platelet-derived growth factor were lower. Histological assessment revealed significant amelioration of the percent medial wall thickness in pulmonary vasculature of rats in the ONONS group. Rats in the ONONS group showed decreased proliferating cell nuclear antigen-positive smooth muscle cells and improved right ventricle pressure/left ventricle pressure. No difference was seen in the accumulation of Texas red-labeled nanoparticles in the brain, heart, liver, and spleen between PAH and normal rats. However, a significant area of nanoparticles was detected in the lungs of PAH rats. ONONS effectively ameliorated PAH, with selective delivery to the damaged lung.
format	article
author	Tomomitsu Kanaya Shigeru Miyagawa Takuji Kawamura Yoshiki Sakai Kenta Masada Nobutoshi Nawa Hidekazu Ishida Jun Narita Koichi Toda Toru Kuratani Yoshiki Sawa
author_facet	Tomomitsu Kanaya Shigeru Miyagawa Takuji Kawamura Yoshiki Sakai Kenta Masada Nobutoshi Nawa Hidekazu Ishida Jun Narita Koichi Toda Toru Kuratani Yoshiki Sawa
author_sort	Tomomitsu Kanaya
title	Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
title_short	Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
title_full	Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
title_fullStr	Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
title_full_unstemmed	Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension
title_sort	innovative therapeutic strategy using prostaglandin i2 agonist (ono1301) combined with nano drug delivery system for pulmonary arterial hypertension
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a0a7092285df41cc9b0a00ae9053c163
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Innovative therapeutic strategy using prostaglandin I2 agonist (ONO1301) combined with nano drug delivery system for pulmonary arterial hypertension

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