In vitro model for evaluating drug transport across the blood-brain barrier

Roméo Cecchelli 1 Bénédicte Dehouck 2 Laurence Descamps 3 Laurence Fenart 1 Valérie Buée-Scherrer 2 C. Duhem Stefan Lundquist M. Rentfel Gérard Torpier Marie-Pierre Dehouck 1
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
2 JPArc - U837 Inserm - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer
3 Pharmacocinétique et Métabolisme Préclinique
Abstract : The passage of substances across the blood-brain barrier (BBB) is regulated in the cerebral capillaries, which possess certain distinct different morphological and enzymatic properties compared with the capillaries of other organs. Investigations of the functional characteristics of brain capillaries have been facilitated by the use of cultured brain endothelial cells, but in most studies some characteristics of the in vivo BBB are lost. To provide an in vitro system for studying brain capillary functions, we have developed a process of coculture that closely mimics the in vivo situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. In order to assess the drug transport across the blood-brain barrier, we compared the extraction ratios in vivo to the permeability of the in vitro model. The in vivo and the in vitro values showed a strong correlation. The relative ease with which such cocultures can be produced in large quantities facilitates the screening of new centrally active drugs. This model provides an easier, reproducible and mass-production method to study the blood-brain barrier in vitro.
Keywords : Brain capillary endothelial cell Astrocyte P-glycoprotein Drug delivery Coculture
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Journal articles
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Submitted on : Wednesday, November 10, 2010 - 3:49:03 PM
Last modification on : Saturday, April 7, 2018 - 2:40:02 PM

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Roméo Cecchelli, Bénédicte Dehouck, Laurence Descamps, Laurence Fenart, Valérie Buée-Scherrer, et al.. In vitro model for evaluating drug transport across the blood-brain barrier. Advanced Drug Delivery Reviews, Elsevier, 1999, 36, p. 165-178. ⟨hal-00534832⟩

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