Physicochemical selectivity of the BBB microenvironment governing passive diffusion--matching with a porcine brain lipid extract artificial membrane permeability model

This study evaluates a PAMPA model based on porcine brain lipid extract (PBLE) to mimic the physicochemical selectivity of the blood–brain barrier (BBB) and predict passive permeability. Using data from over 100 drugs and correlating results with extensive in situ brain perfusion measurements, the authors developed an in combo PAMPA model incorporating permeability and hydrogen-bonding descriptors. The optimized PBLE-PAMPA system demonstrated strong predictive performance and a wide dynamic range, accurately reflecting BBB passive diffusion. Its speed and cost efficiency make it a practical first-pass screening tool for assessing brain penetration in drug discovery.