PT  - JOURNAL ARTICLE
AU  - V. Monnaert
AU  - D. Betbeder
AU  - L. Fenart
AU  - H. Bricout
AU  - A. M. Lenfant
AU  - C. Landry
AU  - R. Cecchelli
AU  - E. Monflier
AU  - S. Tilloy
TI  - Effects of γ- and Hydroxypropyl-γ-cyclodextrins on the Transport of Doxorubicin across an in Vitro Model of Blood-Brain Barrier
AID  - 10.1124/jpet.104.071845
DP  - 2004 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1115--1120
VI  - 311
IP  - 3
4099  - http://jpet.aspetjournals.org/content/311/3/1115.short
4100  - http://jpet.aspetjournals.org/content/311/3/1115.full
SO  - J Pharmacol Exp Ther2004 Dec 01; 311
AB  - Association between doxorubicin (DOX) and γ-cyclodextrin (γ-CD) or hydroxypropyl-γ-CD (HP-γ-CD) has been examined to increase the delivery of this antitumoral agent to the brain. The stoichiometry and the stability constant of γ-CD or HP-γ-CD and DOX complexes were determined in physiological medium by UV-visible spectroscopy. By using an in vitro model of the blood-brain barrier (BBB), endothelial permeability and toxicity toward the brain capillary endothelial cells of DOX, γ-CD, and HP-γ-CD were performed. For each CD, endothelial permeability was relatively low and a disruption of the BBB occurred at 20 μM, 20 mM, and 50 mM DOX, γ-CD, and HP-γ-CD, respectively. Increasing amounts of CDs were added to a fixed DOX concentration. Addition of γ-CD or HP-γ-CD, up to 15 and 35 mM, respectively, decreased the DOX delivery, probably due to the low complex penetration across the BBB and the decrease in free DOX concentration. Higher CD concentrations increased the DOX delivery to the brain, but this effect is due to a loss of BBB integrity. In contrast to what was observed on Caco-2 cell model with various drugs, CDs are not able to increase the delivery of DOX across our in vitro model of BBB. The American Society for Pharmacology and Experimental Therapeutics