Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats
Campos Martorell, Mireia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cano-Sarabia, Mary (Institut Català de Nanociència i Nanotecnologia)
Simats Oriol, Alba (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández Guillamón, María del Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rosell Novel, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Maspoch Comamala, Daniel (Institut Català de Nanociència i Nanotecnologia)
Montaner, Joan (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2016
Abstract:	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. 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. 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. 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.
Grants:	European Commission 202213 European Commission 201024 Ministerio de Economía y Competitividad FIS/11/0176 Instituto de Salud Carlos III FI/10/00508 Instituto de Salud Carlos III CP12/03259 Instituto de Salud Carlos III CP09/00265 Agència de Gestió d'Ajuts Universitaris i de Recerca 2015/FI_B00952
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Simvastatin ; Liposomes ; Delivery ; Brain ; Stroke ; Rat
Published in:	International Journal of Nanomedicine, Vol. 11 (June 2016) , p. 3035-3048, ISSN 1178-2013

DOI: 10.2147/IJN.S107292
PMID: 27418824

14 p, 2.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Catalan Institute of Nanoscience and Nanotechnology (ICN2)
Articles > Research articles
Articles > Published articles