A novel polymer planar biomimetic membrane with self-differentiating intestinal-like structural for drug permeability prediction.

Accurately and efficiently assessing drug permeability has emerged as a critical challenge in early drug discovery and development, prompting the development of various models. In this study, a polymer planar biomimetic membrane permeation assay (PPBMPA) model was established using a Transwell chamber, and its permeability assessment capability was evaluated using model drugs with high, medium, and low permeability. The underlying permeation mechanism was also investigated. The results demonstrated that the biomimetic membrane spontaneously differentiated into an intestinal-like structure comprising a hydrated layer, a polymersome layer, and a basal layer, thereby mimicking the sequential process of drug permeation across the mucus layer, intestinal epithelium, interstitial space, and into the bloodstream. This highly biomimetic permeation pattern enabled effective differentiation between high and low absorption drugs, exhibiting a strong correlation with Caco-2 permeability (R2 = 0.85). Collectively, these findings suggest that the novel PPBMPA model holds promise as a reliable tool for rapid and reproducible drug permeability prediction.