In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain...

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Autores: Estella-Hermoso de Mendoza, A., Préat, Veronique, Mollinedo, Faustino, Blanco-Prieto, María J.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/60755
Acceso en línea:http://hdl.handle.net/10261/60755
Access Level:acceso abierto
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spelling In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against gliomaEstella-Hermoso de Mendoza, A.Préat, VeroniqueMollinedo, FaustinoBlanco-Prieto, María J.Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol (R) and Precirol (R) lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween (R) 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) 14 days after the beginning of the treatment. Our results showed that Tween (R) 80 coated Compritol (R) and Precirol (R) LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo.Caja Navarra Foundation, Ibercaja, the Government of Navarra, Department of Health (“Ortiz de Landázuri” fellowship, ref: 63/09), the Spanish Ministry of Science and Innovation (SAF2007-61261, SAF2008-02251, SAF2010-15547, PCT-090100-2007-27, RD06/0020/1037 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union) and University of Navarra (FUN). Ander Estella-Hermoso de Mendoza is supported by a research grant from the Department of Education of the Basque Government (BFI06.37).Peer ReviewedElsevierRed Temática de Investigación Cooperativa en Cáncer (España)European CommissionMinisterio de Ciencia e Innovación (España)IbercajaFundación Caja NavarraNafarroako GobernuaInstituto de Salud Carlos IIIUniversidad de Navarra2012201220112012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/60755reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/256986http://dx.doi.org/10.1016/j.jconrel.2011.07.030info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/607552026-05-22T06:33:51Z
dc.title.none.fl_str_mv In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
title In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
spellingShingle In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
Estella-Hermoso de Mendoza, A.
title_short In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
title_full In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
title_fullStr In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
title_full_unstemmed In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
title_sort In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma
dc.creator.none.fl_str_mv Estella-Hermoso de Mendoza, A.
Préat, Veronique
Mollinedo, Faustino
Blanco-Prieto, María J.
author Estella-Hermoso de Mendoza, A.
author_facet Estella-Hermoso de Mendoza, A.
Préat, Veronique
Mollinedo, Faustino
Blanco-Prieto, María J.
author_role author
author2 Préat, Veronique
Mollinedo, Faustino
Blanco-Prieto, María J.
author2_role author
author
author
dc.contributor.none.fl_str_mv Red Temática de Investigación Cooperativa en Cáncer (España)
European Commission
Ministerio de Ciencia e Innovación (España)
Ibercaja
Fundación Caja Navarra
Nafarroako Gobernua
Instituto de Salud Carlos III
Universidad de Navarra
description Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol (R) and Precirol (R) lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween (R) 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) 14 days after the beginning of the treatment. Our results showed that Tween (R) 80 coated Compritol (R) and Precirol (R) LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo.
publishDate 2011
dc.date.none.fl_str_mv 2011
2012
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/60755
url http://hdl.handle.net/10261/60755
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language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/EC/FP7/256986
http://dx.doi.org/10.1016/j.jconrel.2011.07.030
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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