Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung

Mari Numata,1 Yelena V Grinkova,2 James R Mitchell,1 Hong Wei Chu,1 Stephen G Sligar,2 Dennis R Voelker1 1Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO, USA; 2Department of Biochemistry, University of Illinois, Urbana, IL, USA Abstract: There is increasing inter...

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Autores principales:	Numata M, Grinkova YV, Mitchell JR, Chu HW, Sligar SG, Voelker DR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/35709cc1895d41f49e070609d2ad7167
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spelling	oai:doaj.org-article:35709cc1895d41f49e070609d2ad71672021-12-02T00:52:04ZNanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung1176-91141178-2013https://doaj.org/article/35709cc1895d41f49e070609d2ad71672013-04-01T00:00:00Zhttp://www.dovepress.com/nanodiscs-as-a-therapeutic-delivery-agent-inhibition-of-respiratory-sy-a12754https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Mari Numata,1 Yelena V Grinkova,2 James R Mitchell,1 Hong Wei Chu,1 Stephen G Sligar,2 Dennis R Voelker1 1Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO, USA; 2Department of Biochemistry, University of Illinois, Urbana, IL, USA Abstract: There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 µg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a half-time of 60–120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo. Keywords: nanodiscs, therapeutic delivery, anti-viral, innate immunity, phospholipidsNumata MGrinkova YVMitchell JRChu HWSligar SGVoelker DRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 1417-1427 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Numata M Grinkova YV Mitchell JR Chu HW Sligar SG Voelker DR Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
description	Mari Numata,1 Yelena V Grinkova,2 James R Mitchell,1 Hong Wei Chu,1 Stephen G Sligar,2 Dennis R Voelker1 1Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, CO, USA; 2Department of Biochemistry, University of Illinois, Urbana, IL, USA Abstract: There is increasing interest in the application of nanotechnology to solve the difficult problem of therapeutic administration of pharmaceuticals. Nanodiscs, composed of a stable discoidal lipid bilayer encircled by an amphipathic membrane scaffold protein that is an engineered variant of the human Apo A-I constituent of high-density lipoproteins, have been a successful platform for providing a controlled lipid composition in particles that are especially useful for investigating membrane protein structure and function. In this communication, we demonstrate that nanodiscs are effective in suppressing respiratory syncytial viral (RSV) infection both in vitro and in vivo when self-assembled with the minor pulmonary surfactant phospholipid palmitoyloleoylphosphatidylglycerol (POPG). Preparations of nanodiscs containing POPG (nPOPG) antagonized interleukin-8 production from Beas2B epithelial cells challenged by RSV infection, with an IC50 of 19.3 µg/mL. In quantitative in vitro plaque assays, nPOPG reduced RSV infection by 93%. In vivo, nPOPG suppressed inflammatory cell infiltration into the lung, as well as IFN-γ production in response to RSV challenge. nPOPG also completely suppressed the histopathological changes in lung tissue elicited by RSV and reduced the amount of virus recovered from lung tissue by 96%. The turnover rate of nPOPG was estimated to have a half-time of 60–120 minutes (m), based upon quantification of the recovery of the human Apo A-I constituent. From these data, we conclude that nPOPG is a potent antagonist of RSV infection and its inflammatory sequelae both in vitro and in vivo. Keywords: nanodiscs, therapeutic delivery, anti-viral, innate immunity, phospholipids
format	article
author	Numata M Grinkova YV Mitchell JR Chu HW Sligar SG Voelker DR
author_facet	Numata M Grinkova YV Mitchell JR Chu HW Sligar SG Voelker DR
author_sort	Numata M
title	Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
title_short	Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
title_full	Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
title_fullStr	Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
title_full_unstemmed	Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
title_sort	nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/35709cc1895d41f49e070609d2ad7167
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Nanodiscs as a therapeutic delivery agent: inhibition of respiratory syncytial virus infection in the lung

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