Tuning the predictive capacity of the PAMPA-BBB model

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Judit MüllerGyörgy T Balogh

Abstract

Due to its robustness and versatility, several variations of the blood-brain barrier specific parallel artificial membrane permeability assay (PAMPA-BBB) have been reported in the central nervous system (CNS) drug discovery practice. In this study, the impact of the main assay parameters on the predictive power of PAMPA-BBB was thoroughly investigated with 27, passively BBB-transported drug molecules with in vivo logBB data. The single and combined effects of the following variables were systematically studied and optimized: incubation time and temperature (4 vs. 18h, RT vs. 37°C), type of the read-out (UV-reader vs. HPLC), solvent composition (n-dodecane/n-hexane), lipid concentration (0-10w/v % PBLE), cholesterol content (0-1.66w/v %), and thickness of the lipid membrane, and the DMSO cosolvent content (5-20v/v %), respectively. Based on our results, solvent-driven and lipid-driven mechanisms of diffusion were identified in different assay conditions. Moreover, the analysis of membrane retention (MR%; the mole fraction of solute "lost" to the membrane) data obtained at various membrane compositions (volume of solvent and concentration of phospholipids) revealed the compound-specific nature of this parameter. The optimized con...Continue Reading

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Citations

Jul 9, 2016·Biomaterials·Juan Aparicio-BlancoAna-Isabel Torres-Suárez
Oct 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lóránd KissIlona Petrikovics
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gábor GirstAttila Hunyadi
Jul 20, 2018·Journal of Agricultural and Food Chemistry·Sandro HofstetterAnke Buchholz
Jun 30, 2018·Molecular Pharmaceutics·Enikő BorbásZsombor K Nagy

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