A surrogate barrier model for high-throughput blood-brain barrier permeability prediction: integrating LLC-PK1-MOCK/MDR1 Cells and lysosomal trapping correction.

ABSTRACT: To mitigate risks in central nervous system (CNS) drug development, we established a high-throughput in vitro blood-brain barrier (BBB) model using LLC-PK1-MOCK and LLC-PK1-MDR1 cells in a Transwell system, aiming to replicate in vivo brain distribution and elucidate permeability mechanisms. Model integrity was assessed via transepithelial electrical resistance (TEER) and efflux functionality using control drugs (atenolol, digoxin). Bidirectional transport studies of 41 compounds quantified permeability (P_app), efflux ratios (ER), and recoveries, while in vivo brain distribution parameters (K_p,uu,brain) were derived from literature and rat studies. The model demonstrated critical BBB features: tight junction integrity (TEER > 70 Ω·cm²), P-gp e

SUBMITTER: Hu J 

PROVIDER: S-EPMC12667295 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature