Ítem
Acceso Abierto

The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cells

Mostrar el registro sencillo de la publicación
dc.creatorPinzón?Daza, MLspa
dc.creatorGarzón, Ruth
dc.creatorCouraud, POspa
dc.creatorRomero, IAspa
dc.creatorWeksler, Bspa
dc.creatorGhigo, Dspa
dc.creatorBosia, Aspa
dc.creatorRiganti, Cspa
dc.date.accessioned2020-05-26T00:03:40Z
dc.date.available2020-05-26T00:03:40Z
dc.date.created2012spa
dc.description.abstractBackground and PurposeThe passage of drugs across the blood-brain barrier (BBB) limits the efficacy of chemotherapy in brain tumours. For instance, the anticancer drug doxorubicin, which is effective against glioblastoma in vitro, has poor efficacy in vivo, because it is extruded by P-glycoprotein (Pgp/ABCB1), multidrug resistance-related proteins and breast cancer resistance protein (BCRP/ABCG2) in BBB cells. The aim of this study was to convert poorly permeant drugs like doxorubicin into drugs able to cross the BBB. Experimental ApproachExperiments were performed on primary human cerebral microvascular endothelial hCMEC/D3 cells, alone and co-cultured with human brain and epithelial tumour cells. Key ResultsStatins reduced the efflux activity of Pgp/ABCB1 and BCRP/ABCG2 in hCMEC/D3 cells by increasing the synthesis of NO, which elicits the nitration of critical tyrosine residues on these transporters. Statins also increased the number of low-density lipoprotein (LDL) receptors exposed on the surface of BBB cells, as well as on tumour cells like human glioblastoma. We showed that the association of statins plus drug-loaded nanoparticles engineered as LDLs was effective as a vehicle for non-permeant drugs like doxorubicin to cross the BBB, allowing its delivery into primary and metastatic brain tumour cells and to achieve significant anti-tumour cytotoxicity. Conclusions and ImplicationsWe suggest that our 'Trojan horse' approach, based on the administration of statins plus a LDL receptor-targeted liposomal drug, might have potential applications in the pharmacological therapy of different brain diseases for which the BBB represents an obstacle. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1111/j.1476-5381.2012.02103.x
dc.identifier.issn71188
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/23615
dc.language.isoengspa
dc.relation.citationEndPage1447
dc.relation.citationIssueNo. 7
dc.relation.citationStartPage1431
dc.relation.citationTitleBritish Journal of Pharmacology
dc.relation.citationVolumeVol. 167
dc.relation.ispartofBritish Journal of Pharmacology, ISSN:71188, Vol.167, No.7 (2012); pp. 1431-1447spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84868660382&doi=10.1111%2fj.1476-5381.2012.02103.x&partnerID=40&md5=3acfbb7f0a9e6cd186fbde38d747ea08spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordBreast cancer resistance proteinspa
dc.subject.keywordldleng
dc.subject.keywordDoxorubicinspa
dc.subject.keywordImmunoglobulin enhancer binding proteinspa
dc.subject.keywordLow density lipoprotein receptorspa
dc.subject.keywordMultidrug resistance proteinspa
dc.subject.keywordNanoparticlespa
dc.subject.keywordNitric oxidespa
dc.subject.keywordRho kinasespa
dc.subject.keywordRhoa guanine nucleotide binding proteinspa
dc.subject.keywordRhoa kinasespa
dc.subject.keywordSimvastatinspa
dc.subject.keywordUnclassified drugspa
dc.subject.keywordArticlespa
dc.subject.keywordBlood brain barrierspa
dc.subject.keywordBrain cellspa
dc.subject.keywordControlled studyspa
dc.subject.keywordDrug cytotoxicityspa
dc.subject.keywordDrug dosage form comparisonspa
dc.subject.keywordDrug efficacyspa
dc.subject.keywordDrug mechanismspa
dc.subject.keywordDrug penetrationspa
dc.subject.keywordDrug potentiationspa
dc.subject.keywordDrug receptor bindingspa
dc.subject.keywordDrug transportspa
dc.subject.keywordEnzyme activityspa
dc.subject.keywordGlioblastomaspa
dc.subject.keywordHumanspa
dc.subject.keywordHuman cellspa
dc.subject.keywordIn vitro studyspa
dc.subject.keywordLiposomal deliveryspa
dc.subject.keywordMicrovascular endothelial cellspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein expressionspa
dc.subject.keywordTumor cell linespa
dc.subject.keywordAtp-binding cassette transportersspa
dc.subject.keywordBlood-brain barrierspa
dc.subject.keywordCell linespa
dc.subject.keywordCell lineeng
dc.subject.keywordDoxorubicinspa
dc.subject.keywordHumansspa
dc.subject.keywordHydroxymethylglutaryl-coa reductase inhibitorsspa
dc.subject.keywordLiposomesspa
dc.subject.keywordLovastatinspa
dc.subject.keywordNf-kappa bspa
dc.subject.keywordNitric oxide synthasespa
dc.subject.keywordNitritesspa
dc.subject.keywordReceptorseng
dc.subject.keywordRho-associated kinasesspa
dc.subject.keywordRhoa gtp-binding proteinspa
dc.subject.keywordSimvastatinspa
dc.subject.keywordAtp-binding cassette transportersspa
dc.subject.keywordBlood-brain barrierspa
dc.subject.keywordCentral nervous system tumoursspa
dc.subject.keywordDoxorubicinspa
dc.subject.keywordLiposomesspa
dc.subject.keywordLow-density lipoproteins receptorspa
dc.subject.keywordNitric oxidespa
dc.subject.keywordStatinsspa
dc.titleThe association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood-brain barrier cellsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
Archivos
Bloque original
Mostrando1 - 1 de 1
Miniatura
Nombre:
j-1476-5381-2012-02103-x.pdf
Tamaño:
2.84 MB
Formato:
Adobe Portable Document Format
Descripción:
Descargar
Colecciones
Artículos