In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

Torben Gjetting1, Nicolai Skovbjerg Arildsen1, Camilla Laulund Christensen1, Thomas Tuxen Poulsen1, Jack A Roth3, Vagn Neerup Handlos2, Hans Skovgaard Poulsen11Department of Radiation Biology, Finsen Center, 2RH Pharmacy, Copenhagen University Hospital, Copenhagen, Denmark; 3Thoracic Medical Oncolog...

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Autores principales:	Torben Gjetting, Nicolai Skovbjerg Arildsen, Camilla Laulund, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5cba136f886f4df5a6c23c19be1a6fda
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spelling	oai:doaj.org-article:5cba136f886f4df5a6c23c19be1a6fda2021-12-02T00:40:21ZIn vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection1176-91141178-2013https://doaj.org/article/5cba136f886f4df5a6c23c19be1a6fda2010-05-01T00:00:00Zhttp://www.dovepress.com/in-vitro-and-in-vivo-effects-of-polyethylene-glycol-peg-modified-lipid-a4502https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Torben Gjetting1, Nicolai Skovbjerg Arildsen1, Camilla Laulund Christensen1, Thomas Tuxen Poulsen1, Jack A Roth3, Vagn Neerup Handlos2, Hans Skovgaard Poulsen11Department of Radiation Biology, Finsen Center, 2RH Pharmacy, Copenhagen University Hospital, Copenhagen, Denmark; 3Thoracic Medical Oncology, MD Anderson Cancer Centre, Houston, TX, USABackground: DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream.Method: A direct comparison of properties in vitro and in vivo of 4 different DOTAP/cholesterol-based lipoplexes containing 0%, 2%, 4%,&nbsp;and 10% PEG was performed using reporter gene activity and radioactive tracer lipid markers to monitor biodistribution.Results: We found that 10% PEGylation of lipoplexes caused reduced retention in lung and heart tissues of nude mice compared to nonPEGylated lipoplexes, however no significant delivery to xenograft flank tumors was observed. Although PEGylated and nonPEGylated lipoplexes were delivered to cells the ability to mediate successful transfection is hampered upon PEGylation, presumably due to a changed uptake mechanism and intracellular processing.Conclusion: The eminent in vivo transfection potency of DOTAP/cholesterol-based lipoplexes is well established for expression in lung tumors, but it is unsuitable for expression in non first pass organs such as xenograft flank tumors in mice even after addition of a PEG-lipid in the formulation.Keywords: gene delivery, DOTAP, polyethylene glycol (PEG), biodistribution, lung cancer, xenograft tumor model Torben GjettingNicolai Skovbjerg ArildsenCamilla Laulundet alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 371-383 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Torben Gjetting Nicolai Skovbjerg Arildsen Camilla Laulund et al In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
description	Torben Gjetting1, Nicolai Skovbjerg Arildsen1, Camilla Laulund Christensen1, Thomas Tuxen Poulsen1, Jack A Roth3, Vagn Neerup Handlos2, Hans Skovgaard Poulsen11Department of Radiation Biology, Finsen Center, 2RH Pharmacy, Copenhagen University Hospital, Copenhagen, Denmark; 3Thoracic Medical Oncology, MD Anderson Cancer Centre, Houston, TX, USABackground: DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream.Method: A direct comparison of properties in vitro and in vivo of 4 different DOTAP/cholesterol-based lipoplexes containing 0%, 2%, 4%,&nbsp;and 10% PEG was performed using reporter gene activity and radioactive tracer lipid markers to monitor biodistribution.Results: We found that 10% PEGylation of lipoplexes caused reduced retention in lung and heart tissues of nude mice compared to nonPEGylated lipoplexes, however no significant delivery to xenograft flank tumors was observed. Although PEGylated and nonPEGylated lipoplexes were delivered to cells the ability to mediate successful transfection is hampered upon PEGylation, presumably due to a changed uptake mechanism and intracellular processing.Conclusion: The eminent in vivo transfection potency of DOTAP/cholesterol-based lipoplexes is well established for expression in lung tumors, but it is unsuitable for expression in non first pass organs such as xenograft flank tumors in mice even after addition of a PEG-lipid in the formulation.Keywords: gene delivery, DOTAP, polyethylene glycol (PEG), biodistribution, lung cancer, xenograft tumor model
format	article
author	Torben Gjetting Nicolai Skovbjerg Arildsen Camilla Laulund et al
author_facet	Torben Gjetting Nicolai Skovbjerg Arildsen Camilla Laulund et al
author_sort	Torben Gjetting
title	In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
title_short	In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
title_full	In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
title_fullStr	In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
title_full_unstemmed	In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection
title_sort	in vitro and in vivo effects of polyethylene glycol (peg)-modified lipid in dotap/cholesterol-mediated gene transfection
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/5cba136f886f4df5a6c23c19be1a6fda
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In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

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