Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Insti...

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Autores principales:	Campos-Martorell M, Cano-Sarabia M, Simats A, Hernández-Guillamon M, Rosell A, Maspoch D, Montaner J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Simvastatin liposomes delivery brain stroke rat Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/10fa5584a04d479e8a1ae4cfb2ae6464
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spelling	oai:doaj.org-article:10fa5584a04d479e8a1ae4cfb2ae64642021-12-02T05:01:06ZCharge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats1178-2013https://doaj.org/article/10fa5584a04d479e8a1ae4cfb2ae64642016-06-01T00:00:00Zhttps://www.dovepress.com/charge-effect-of-a-liposomal-delivery-system-encapsulating-simvastatin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA), 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV) administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes were able to reach the brain and accumulate specifically in the infarcted area. Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered. The detection of simvastatin by ultra-high-protein liquid chromatography confirmed its ability to cross the blood–brain barrier, when administered either as a free drug or encapsulated into liposomes. Conclusion: This study confirms that liposome charge is critical to promote its accumulation in the brain infarct after MCAOt. Furthermore, simvastatin can be delivered after being encapsulated. Thus, simvastatin encapsulation might be a promising strategy to ensure that the drug reaches the brain, while increasing its bioavailability and reducing possible side effects. Keywords: simvastatin, liposomes, delivery, brain, stroke, ratCampos-Martorell MCano-Sarabia MSimats AHernández-Guillamon MRosell AMaspoch DMontaner JDove Medical PressarticleSimvastatinliposomesdeliverybrainstrokeratMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3035-3048 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Simvastatin liposomes delivery brain stroke rat Medicine (General) R5-920
spellingShingle	Simvastatin liposomes delivery brain stroke rat Medicine (General) R5-920 Campos-Martorell M Cano-Sarabia M Simats A Hernández-Guillamon M Rosell A Maspoch D Montaner J Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
description	Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA), 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt) surgery and treated (intravenous [IV]) with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV) administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes were able to reach the brain and accumulate specifically in the infarcted area. Moreover, neutral liposomes exhibited higher bioavailability in plasma 4 hours after being administered. The detection of simvastatin by ultra-high-protein liquid chromatography confirmed its ability to cross the blood–brain barrier, when administered either as a free drug or encapsulated into liposomes. Conclusion: This study confirms that liposome charge is critical to promote its accumulation in the brain infarct after MCAOt. Furthermore, simvastatin can be delivered after being encapsulated. Thus, simvastatin encapsulation might be a promising strategy to ensure that the drug reaches the brain, while increasing its bioavailability and reducing possible side effects. Keywords: simvastatin, liposomes, delivery, brain, stroke, rat
format	article
author	Campos-Martorell M Cano-Sarabia M Simats A Hernández-Guillamon M Rosell A Maspoch D Montaner J
author_facet	Campos-Martorell M Cano-Sarabia M Simats A Hernández-Guillamon M Rosell A Maspoch D Montaner J
author_sort	Campos-Martorell M
title	Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
title_short	Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
title_full	Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
title_fullStr	Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
title_full_unstemmed	Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
title_sort	charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/10fa5584a04d479e8a1ae4cfb2ae6464
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Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

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