Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins

Abstract Acute lung injury (ALI) leads to progressive loss of breathing capacity and hypoxemia, as well as pulmonary surfactant dysfunction. ALI’s pathogenesis and management are complex, and it is a significant cause of morbidity and mortality worldwide. Exogenous surfactant therapy, even for resea...

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Autores principales:	Ann M. Czyzewski, Lynda M. McCaig, Michelle T. Dohm, Lauren A. Broering, Li-Juan Yao, Nathan J. Brown, Maruti K. Didwania, Jennifer S. Lin, Jim F. Lewis, Ruud Veldhuizen, Annelise E. Barron
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a096b460ffa43f2a9f1d30deb079393
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spelling	oai:doaj.org-article:5a096b460ffa43f2a9f1d30deb0793932021-12-02T15:08:39ZEffective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins10.1038/s41598-018-25009-32045-2322https://doaj.org/article/5a096b460ffa43f2a9f1d30deb0793932018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25009-3https://doaj.org/toc/2045-2322Abstract Acute lung injury (ALI) leads to progressive loss of breathing capacity and hypoxemia, as well as pulmonary surfactant dysfunction. ALI’s pathogenesis and management are complex, and it is a significant cause of morbidity and mortality worldwide. Exogenous surfactant therapy, even for research purposes, is impractical for adults because of the high cost of current surfactant preparations. Prior in vitro work has shown that poly-N-substituted glycines (peptoids), in a biomimetic lipid mixture, emulate key biophysical activities of lung surfactant proteins B and C at the air-water interface. Here we report good in vivo efficacy of a peptoid-based surfactant, compared with extracted animal surfactant and a synthetic lipid formulation, in a rat model of lavage-induced ALI. Adult rats were subjected to whole-lung lavage followed by administration of surfactant formulations and monitoring of outcomes. Treatment with a surfactant protein C mimic formulation improved blood oxygenation, blood pH, shunt fraction, and peak inspiratory pressure to a greater degree than surfactant protein B mimic or combined formulations. All peptoid-enhanced treatment groups showed improved outcomes compared to synthetic lipids alone, and some formulations improved outcomes to a similar extent as animal-derived surfactant. Robust biophysical mimics of natural surfactant proteins may enable new medical research in ALI treatment.Ann M. CzyzewskiLynda M. McCaigMichelle T. DohmLauren A. BroeringLi-Juan YaoNathan J. BrownMaruti K. DidwaniaJennifer S. LinJim F. LewisRuud VeldhuizenAnnelise E. BarronNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ann M. Czyzewski Lynda M. McCaig Michelle T. Dohm Lauren A. Broering Li-Juan Yao Nathan J. Brown Maruti K. Didwania Jennifer S. Lin Jim F. Lewis Ruud Veldhuizen Annelise E. Barron Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
description	Abstract Acute lung injury (ALI) leads to progressive loss of breathing capacity and hypoxemia, as well as pulmonary surfactant dysfunction. ALI’s pathogenesis and management are complex, and it is a significant cause of morbidity and mortality worldwide. Exogenous surfactant therapy, even for research purposes, is impractical for adults because of the high cost of current surfactant preparations. Prior in vitro work has shown that poly-N-substituted glycines (peptoids), in a biomimetic lipid mixture, emulate key biophysical activities of lung surfactant proteins B and C at the air-water interface. Here we report good in vivo efficacy of a peptoid-based surfactant, compared with extracted animal surfactant and a synthetic lipid formulation, in a rat model of lavage-induced ALI. Adult rats were subjected to whole-lung lavage followed by administration of surfactant formulations and monitoring of outcomes. Treatment with a surfactant protein C mimic formulation improved blood oxygenation, blood pH, shunt fraction, and peak inspiratory pressure to a greater degree than surfactant protein B mimic or combined formulations. All peptoid-enhanced treatment groups showed improved outcomes compared to synthetic lipids alone, and some formulations improved outcomes to a similar extent as animal-derived surfactant. Robust biophysical mimics of natural surfactant proteins may enable new medical research in ALI treatment.
format	article
author	Ann M. Czyzewski Lynda M. McCaig Michelle T. Dohm Lauren A. Broering Li-Juan Yao Nathan J. Brown Maruti K. Didwania Jennifer S. Lin Jim F. Lewis Ruud Veldhuizen Annelise E. Barron
author_facet	Ann M. Czyzewski Lynda M. McCaig Michelle T. Dohm Lauren A. Broering Li-Juan Yao Nathan J. Brown Maruti K. Didwania Jennifer S. Lin Jim F. Lewis Ruud Veldhuizen Annelise E. Barron
author_sort	Ann M. Czyzewski
title	Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
title_short	Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
title_full	Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
title_fullStr	Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
title_full_unstemmed	Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
title_sort	effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/5a096b460ffa43f2a9f1d30deb079393
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Effective in vivo treatment of acute lung injury with helical, amphipathic peptoid mimics of pulmonary surfactant proteins

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