Validation of an immortalized human (hBMEC) in vitro blood-brain barrier model

Analytical and Bioanalytical Chemistry
Daniela E EigenmannMouhssin Oufir

Abstract

We recently established and optimized an immortalized human in vitro blood-brain barrier (BBB) model based on the hBMEC cell line. In the present work, we validated this mono-culture 24-well model with a representative series of drug substances which are known to cross or not to cross the BBB. For each individual compound, a quantitative UHPLC-MS/MS method in Ringer HEPES buffer was developed and validated according to current regulatory guidelines, with respect to selectivity, precision, and reliability. Various biological and analytical challenges were met during method validation, highlighting the importance of careful method development. The positive controls antipyrine, caffeine, diazepam, and propranolol showed mean endothelial permeability coefficients (P e) in the range of 17-70 × 10(-6) cm/s, indicating moderate to high BBB permeability when compared to the barrier integrity marker sodium fluorescein (mean P e 3-5 × 10(-6) cm/s). The negative controls atenolol, cimetidine, and vinblastine showed mean P e values < 10 × 10(-6) cm/s, suggesting low permeability. In silico calculations were in agreement with in vitro data. With the exception of quinidine (P-glycoprotein inhibitor and substrate), BBB permeability of all con...Continue Reading

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Citations

Mar 29, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Daniela Elisabeth EigenmannMouhssin Oufir
Nov 21, 2017·European Journal of Nutrition·Inês FigueiraCláudia N Santos
Jul 15, 2018·Nature Communications·Brunilde GrilPatricia S Steeg
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May 10, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Massoud SaidijamSimon G Patching
Sep 15, 2017·Scientific Reports·I FigueiraC N Santos
Nov 2, 2017·Fluids and Barriers of the CNS·Xiaomei ChenMargareta Hammarlund-Udenaes

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