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
- Unité mixte Institut Pasteur de Lille-Universitéd'Artois, Faculté des sciences Jean-Perrin, Lens, France
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.
Footnotes
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Send reprint requests to: Roméo Cecchelli, Unité mixte Institut Pasteur-Université d'Artois, Faculté des sciences Jean-Perrin, 62307 Lens, France. E-mail:romeo.cecchelli{at}pasteur-lille.fr
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↵1 Current address: Biovector Therapeutics, Chemin du Chêne vert, BP 169, 31676 Labège cedex, France.
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↵2 Current address: Institut National de la Santé et de la Recherche Médicale U325, Département d'Athérosclérose, Institut Pasteur de Lille, 59019 Lille, France.
- Abbreviations:
- BBB
- blood-brain barrier
- EC
- endothelial cell
- L-BV
- light biovector
- PC
- polysaccharide core
- QAE
- cationic
- N
- neutral
- P
- anionic
- LDL
- low-density lipoprotein
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- Received June 7, 1999.
- Accepted August 17, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
