Methylated beta-cyclodextrin as P-gp modulators for deliverance of doxorubicin across an in vitro model of blood-brain barrier.
Co-incubations of various beta-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-beta-cyclodextrin and Crysme-beta-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.
Tilloy
Sébastien
S
Blood-Brain Barrier Laboratory, Université d'Artois, EA 2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, SP 18, 62307 Lens Cedex, France. sebastien.tilloy@univ-artois.fr
Monnaert
Véronique
V
Fenart
Laurence
L
Bricout
Hervé
H
Cecchelli
Roméo
R
Monflier
Eric
E
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D008745:Methylation; D051381:Rats; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000494:pharmacology*
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D004317:Doxorubicin; C031215:betadex