PT  - JOURNAL ARTICLE
AU  - L. Fenart
AU  - A. Casanova
AU  - B. Dehouck
AU  - C. Duhem
AU  - S. Slupek
AU  - R. Cecchelli
AU  - D. Betbeder
TI  - 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
DP  - 1999 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1017--1022
VI  - 291
IP  - 3
4099  - http://jpet.aspetjournals.org/content/291/3/1017.short
4100  - http://jpet.aspetjournals.org/content/291/3/1017.full
SO  - J Pharmacol Exp Ther1999 Dec 01; 291
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics