PT  - JOURNAL ARTICLE
AU  - V. Monnaert
AU  - S. Tilloy
AU  - H. Bricout
AU  - L. Fenart
AU  - R. Cecchelli
AU  - E. Monflier
TI  - Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier
AID  - 10.1124/jpet.104.067512
DP  - 2004 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 745--751
VI  - 310
IP  - 2
4099  - http://jpet.aspetjournals.org/content/310/2/745.short
4100  - http://jpet.aspetjournals.org/content/310/2/745.full
SO  - J Pharmacol Exp Ther2004 Aug 01; 310
AB  - Cyclodextrins (CDs) can be envisaged to cure some diseases related to the brain, but the behavior of these compounds toward the blood-brain barrier (BBB) remains largely unexplored to envisage such clinical applications. To fulfill this gap, the toxicity and endothelial permeability for native, methylated, and hydroxypropylated α-, β-, and γ-CDs have been studied on an in vitro model of BBB. As shown by the endothelial permeability for sucrose and immunofluorescence stainings, the native CDs are the most toxic CDs (α- > β- > γ-CD). Whereas the chemical modification of β-CD did not affect the toxicity of this CD, differences are observed for the α- and γ-CD. To determine the origin of toxicity, lipid effluxes on the brain capillary endothelial cells were performed in the presence of native CDs. It was found that α-CD removed phospholipids and that β-CD extracted phospholipids and cholesterol. γ-CD was less lipid-selective than the other CDs. Finally, the endothelial permeability of each CD has been determined. Surprisingly, no structure/permeability relationship has been observed according to the nature and chemical modifications of CDs. The American Society for Pharmacology and Experimental Therapeutics