Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier

Laurence Fenart 1 A. Casanova Bénédicte Dehouck 2 C. Duhem Stéphanie Slupek Roméo Cecchelli 1 Didier Betbeder 3
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
2 JPArc - U837 Inserm - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer
3 Biologie et physiologie des états septiques
Abstract : A cell culture model of the blood-brain barrier (BBB) consisting of a coculture of bovine brain capillary endothelial cells and rat astrocytes has been used to examine the ability of 60-nm nanoparticles with different physicochemical characteristics to cross the BBB. Neutral, anionic, and cationic nanoparticles were made from crosslinked malto-dextrins derivatized or not (neutral) with phosphates (anionic), quaternary ammoniums (cationic) ligands. Then, these particles were coated or not with a lipid bilayer made of dipalmitoyl phosphatidyl choline and cholesterol. Lipid coating of ionically charged nanoparticles was able to increase BBB crossing 3- or 4-fold compared with uncoated particles, whereas coating of neutral particles did not significantly alter their permeation characteristics across the endothelial cell monolayer. Lipid-coated nanoparticles were nontoxic toward BBB integrity, and crossed the BBB by transcytosis without any degradation. Furthermore, a 27-fold increase in albumin transport was observed when albumin had previously been loaded in the cationic lipid-coated nanoparticles. The influence of red blood cells was studied; a marked inhibition of the transport was observed, probably due to strong interaction between nanoparticles and red blood cells.
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Submitted on : Wednesday, November 10, 2010 - 3:19:48 PM
Last modification on : Monday, July 22, 2019 - 9:12:04 AM

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Laurence Fenart, A. Casanova, Bénédicte Dehouck, C. Duhem, Stéphanie Slupek, et al.. Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. Journal of Pharmacology and Experimental Therapeutics, American Society for Pharmacology and Experimental Therapeutics, 1999, 291 (3), p. 1017-1022. ⟨hal-00534808⟩

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