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Title: Translocating the blood-brain barrier using electrostatics
Authors: Ribeiro, Marta M. B.
Domingues, Marco M.
Freire, João M.
Santos, Nuno C.
Castanho, Miguel A. R. B.
Keywords: Blood-brain barrier
Drug targeting
Blood cells
Cell surface charge
Issue Date: 2012
Publisher: Frontiers Research Foundation
Citation: Frontiers in Cellular Neuroscience October 2012 | Volume6 | Article44 | 1-7
Abstract: Mammalian 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.
Description: Copyright © 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.
Peer review: yes
ISSN: 1662-5102
Publisher Version: This document is protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission
Appears in Collections:IMM - Artigos em Revistas Internacionais

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