An in vitro model for blood brain barrier permeation

Author(s)
Roland Bauer, Regina Lauer, Birgit Linz, Fritz Pittner, Günter Peschek, Gerhard Ecker, Peter Friedl, Christian Noe
Abstract

The ability to permeate accross the blood brain barrier (BBB) is essential for drugs acting on the central nervous system (CNS). Thus, systems that allow rapid and inexpensive screening of the BBB-permeability properties of novel lead compounds are of great importance for speeding up the drug discovery process in the CNS-area. We used immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) to develop a model for measurement of blood-brain barrier permeation of CNS active drugs. Investigation of different cell culture conditions showed, that a system using C6 astrocyte glioma conditioned medium and addition of a cyclic AMP analog in combination with a type IV phosphodiesterase inhibitor (RO20-1724) leads to cell layers with transendothelial electrical resistance values up to 300 Ocm2. Permeability studies with U-[14C] sucrose gave a permeability coefficient Pc of 3.24 ‘ 0.14 × 10-4 cm/min, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro.

Organisation(s)
Department of Biochemistry and Cell Biology, Department of Physical Chemistry
External organisation(s)
Johann Wolfgang Goethe-Universität Frankfurt am Main, Universität Wien, Technische Universität Darmstadt
Journal
Scientia Pharmaceutica
Volume
70
Pages
317-324
No. of pages
8
ISSN
0036-8709
DOI
https://doi.org/10.3797/scipharm.aut-02-30
Publication date
2002
Peer reviewed
Yes
Austrian Fields of Science 2012
3012 Pharmacy, Pharmacology, Toxicology
Portal url
https://ucris.univie.ac.at/portal/en/publications/an-in-vitro-model-for-blood-brain-barrier-permeation(2a1eaa7a-af47-4e70-a81c-f4e5d6598b6d).html