INTRODUCTION: BBB models are increasingly used to evaluate barrier properties and drug transport, but platform variability and limited standardization hinder consistent interpretation and translational use. AREAS COVERED: BBB models for CNS drug development, focusing on static, dynamic, microfluidic, induced pluripotent stem cell-derived, and three-dimensional (3D) BBB platforms. Emphasis is placed on model applicability for permeability assessment, transporter activity, exposure kinetics, spatial distribution, and translational prediction. Relevant literature was searched using PubMed, Web of Science, and Google Scholar up to 2025. EXPERT OPINION: BBB. The major limitation is persistent inconsistency across models, which complicates interpretation and limits confidence in their translational application. Static models are practical but provide only partial representation of BBB function, whereas stem cell-based and microfluidic platforms offer greater physiological relevance but face reproducibility and scalability challenges. Future progress should prioritize context-of-use-driven model selection, tiered validation, and harmonized reporting to support reliable decision-making in CNS drug development.
Lee et al. (Mon,) studied this question.