A microfluidic biomimetic system from the blood-brain barrier to activated microglia towards anti-Mesial Temporal Lobe Epilepsy drug screening #MMPMID41390586
Wang Y; Du M; Xie Z; Chen H; Lu L; Jiang L; Wang L; Zheng G
Anal Bioanal Chem 2025[Dec]; ? (?): ? PMID41390586show ga
The development of drugs for mesial temporal lobe epilepsy (mTLE) is hampered by the absence of preclinical models that can concurrently evaluate blood-brain barrier (BBB) penetration and target efficacy. To bridge critical gaps in preclinical screening, we developed an integrated microfluidic microBBB-(KA-MG)-mTLE chip that simultaneously models a perfusable human BBB under physiological shear stress (0.03-2.04 dyn/cm(2)) and a neuroinflammatory mTLE microenvironment with activated microglia. This platform enabled the dual-parameter assessment of drug candidates, quantifying their BBB permeability and anti-inflammatory activity in a single experiment. In a practical screening application, osthole was identified as a promising candidate for its adequate brain exposure and potent efficacy, whereas a high molecular weight grape seed extract showed activity only when bypassing the BBB, demonstrating the platform's critical ability to de-risk candidate selection. Our biomimetic system provides a transformative tool for anti-epileptic drug discovery by integrating pharmacokinetic and pharmacodynamic evaluation.
Anal+Bioanal+Chem 2025 ; ? (?): ?
