Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles

Jasmin Matuszak, Barbara Lutz, Aleksander Sekita, Jan Zaloga, Christoph Alexiou, Stefan Lyer,* Iwona Cicha* Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-endowed Professorship for Nanomedicine, ENT Department, Uni...

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Autores principales:	Matuszak J, Lutz B, Sekita A, Zaloga J, Alexiou C, Lyer S, Cicha I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	magnetic nanoparticles magnetic drug targeting rabbit model of atherosclerosis dexamethasone macrophage accumulation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b034598c49334bd49c1363942e45a814
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spelling	oai:doaj.org-article:b034598c49334bd49c1363942e45a8142021-12-02T06:07:13ZDrug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles1178-2013https://doaj.org/article/b034598c49334bd49c1363942e45a8142018-12-01T00:00:00Zhttps://www.dovepress.com/drug-delivery-to-atherosclerotic-plaques-using-superparamagnetic-iron--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jasmin Matuszak, Barbara Lutz, Aleksander Sekita, Jan Zaloga, Christoph Alexiou, Stefan Lyer,* Iwona Cicha* Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-endowed Professorship for Nanomedicine, ENT Department, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany *These authors contributed equally to this work Introduction: Magnetic drug targeting utilizes superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate drugs in specified vasculature regions.Methods: We produced SPIONs conjugated with dexamethasone phosphate (SPION-DEXA). The efficacy of magnetic drug targeting was investigated in a rabbit model of atherosclerosis induced by balloon injury and high cholesterol diet.Results: In vitro, SPION-DEXA were well-tolerated by endothelial cells. SPION-DEXA were internalized by human peripheral blood mononuclear cells and induced CD163 expression comparable with the free drug. In vivo, magnetic targeting of SPIONs to abdominal aorta was confirmed by histology. Upon vascular injury followed by high-cholesterol diet, early administration of SPION-DEXA enhanced the inflammatory burden in the plaques. Increased macrophage content and larger intima–media thickness were observed in animals treated with SPION-DEXA compared with controls. In advanced atherosclerosis, no beneficial effect of local glucocorticoid therapy was detectable.Conclusion: Magnetic drug targeting represents an efficient platform to deliver drugs to diseased arteries in vivo. However, targeting of vascular injury in the lipid-rich environment using dexamethasone-conjugated SPIONs may cause accelerated inflammatory response. Keywords: magnetic nanoparticles, magnetic drug targeting, rabbit model of atherosclerosis, dexamethasone, macrophage accumulationMatuszak JLutz BSekita AZaloga JAlexiou CLyer SCicha IDove Medical Pressarticlemagnetic nanoparticlesmagnetic drug targetingrabbit model of atherosclerosisdexamethasonemacrophage accumulationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8443-8460 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	magnetic nanoparticles magnetic drug targeting rabbit model of atherosclerosis dexamethasone macrophage accumulation Medicine (General) R5-920
spellingShingle	magnetic nanoparticles magnetic drug targeting rabbit model of atherosclerosis dexamethasone macrophage accumulation Medicine (General) R5-920 Matuszak J Lutz B Sekita A Zaloga J Alexiou C Lyer S Cicha I Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
description	Jasmin Matuszak, Barbara Lutz, Aleksander Sekita, Jan Zaloga, Christoph Alexiou, Stefan Lyer,* Iwona Cicha* Cardiovascular Nanomedicine Unit, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-endowed Professorship for Nanomedicine, ENT Department, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany *These authors contributed equally to this work Introduction: Magnetic drug targeting utilizes superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate drugs in specified vasculature regions.Methods: We produced SPIONs conjugated with dexamethasone phosphate (SPION-DEXA). The efficacy of magnetic drug targeting was investigated in a rabbit model of atherosclerosis induced by balloon injury and high cholesterol diet.Results: In vitro, SPION-DEXA were well-tolerated by endothelial cells. SPION-DEXA were internalized by human peripheral blood mononuclear cells and induced CD163 expression comparable with the free drug. In vivo, magnetic targeting of SPIONs to abdominal aorta was confirmed by histology. Upon vascular injury followed by high-cholesterol diet, early administration of SPION-DEXA enhanced the inflammatory burden in the plaques. Increased macrophage content and larger intima–media thickness were observed in animals treated with SPION-DEXA compared with controls. In advanced atherosclerosis, no beneficial effect of local glucocorticoid therapy was detectable.Conclusion: Magnetic drug targeting represents an efficient platform to deliver drugs to diseased arteries in vivo. However, targeting of vascular injury in the lipid-rich environment using dexamethasone-conjugated SPIONs may cause accelerated inflammatory response. Keywords: magnetic nanoparticles, magnetic drug targeting, rabbit model of atherosclerosis, dexamethasone, macrophage accumulation
format	article
author	Matuszak J Lutz B Sekita A Zaloga J Alexiou C Lyer S Cicha I
author_facet	Matuszak J Lutz B Sekita A Zaloga J Alexiou C Lyer S Cicha I
author_sort	Matuszak J
title	Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
title_short	Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
title_full	Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
title_fullStr	Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
title_full_unstemmed	Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
title_sort	drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/b034598c49334bd49c1363942e45a814
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Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles

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