Methylated β-cyclodextrin as P-gp modulators for deliverance of doxorubicin across an in vitro model of blood-brain barrier

Sébastien Tilloy (1) , Véronique Monnaert (2) , Laurence Fenart (2) , Hervé Bricout (1) , Roméo Cecchelli (2) , Eric Monflier (3)

1 Laboratoire de Physico-Chimie des Interfaces et Applications
2 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
3 UCCS Artois - Unité de Catalyse et Chimie du Solide - Equipes du Site Artois

Co-incubations of various β-cyclodextrins and doxorubicin have been evaluated on an in vitro model of blood-brain barrier in order to increase the delivery of this P-gp substrate to the brain. Among these cyclodextrins used, the Rame-β-cyclodextrin and Crysme-β-cyclodextrin increased the transport by a factor of 2 and 3.7, respectively. This increase was attributed to the cholesterol extraction property of these cyclodextrins from brain capillary endothelial cells leading to a modulation of the P-gp activity.

Keywords: Cyclodextrin; Doxorubicin; P-glycoprotein; Blood-brain barrier; Cholesterol

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology

Sébastien Tilloy, Véronique Monnaert, Laurence Fenart, Hervé Bricout, Roméo Cecchelli, et al.. Methylated β-cyclodextrin as P-gp modulators for deliverance of doxorubicin across an in vitro model of blood-brain barrier. Bioorganic and Medicinal Chemistry Letters, 2006, 16, p. 2154-2157. ⟨hal-00543357⟩