An in vitro model for blood brain barrier permeation

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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 Ωcm2. 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.

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Bauer, R., Lauer, R., Linz, B., Pittner, F., Peschek, G. A., Ecker, G. F., … Noe, C. R. (2002). An in vitro model for blood brain barrier permeation. Scientia Pharmaceutica, 70(4), 317–324. https://doi.org/10.3797/scipharm.aut-02-30

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