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Translocating the blood-brain barrier using electrostatics

dc.contributor.authorRibeiro, Marta M. B.
dc.contributor.authorDomingues, Marco M.
dc.contributor.authorFreire, João M.
dc.contributor.authorSantos, Nuno C.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.date.accessioned2012-11-28T16:11:20Z
dc.date.available2012-11-28T16:11:20Z
dc.date.issued2012
dc.descriptionCopyright © 2012 Ribeiro,Domingues, Freire,Santos and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.eng
dc.description.abstractMammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC).To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier.eng
dc.description.sponsorshipFundação para a Ciência e Tecnologia — Ministério da Educação e Ciência (FCT-MEC, Portugal) is acknowledged for funding (including fellowships SFRH/BD/42158/2007 to Marta M.B. Ribeiro, SFRH/BD/41750/2007 to Marco M. Domingues and SFRH/BD/70423/2010 to João M. Freire) and project PTDC/QUI-BIQ/119509/2010. Marie Curie Industry-Academia Partnerships and Pathways (European Commission) is also acknowledged for funding (FP7-PEOPLE-2007-3-1-IAPP, Project 230654).eng
dc.identifier.citationFrontiers in Cellular Neuroscience October 2012 | Volume6 | Article44 | 1-7eng
dc.identifier.issn1662-5102
dc.identifier.urihttp://dx.doi.org/10.3389/fncel.2012.00044
dc.identifier.urihttp://hdl.handle.net/10451/7309
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherFrontiers Research Foundationeng
dc.relation.publisherversionThis document is protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissioneng
dc.subjectBlood-brain barriereng
dc.subjectDrug targetingeng
dc.subjectBlood cellseng
dc.subjectCell surface chargeeng
dc.subjectZeta-potentialeng
dc.titleTranslocating the blood-brain barrier using electrostaticseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage7por
oaire.citation.startPage1por
oaire.citation.titleFrontiers in Cellular Neuroscienceeng
oaire.citation.volume6por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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