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

Abstract

Accurately and efficiently assessing the drug permeability are emerging as the big challenge early in new drug discovery and development, thus various models have been developed. Here, a polymer planar biomimetic membrane permeation assay (PPBMPA) model was constructed in a transwell chamber, and the ability to assess permeability of this in vitro model was investigated by model drugs with high, medium, and low permeability. Meanwhile, the mechanism for predicting the drug permeability of this model were also investigated. The results showed that the biomimetic membrane in this model was capable of self-differentiating to form an intestinal-like structure, including a hydrated layer, a polymersome layer, and a basal layer, thus simulating the process for drug passing through the mucus layer, intestinal epithelial cell layer, tissue interstitial space, and finally entering into the blood. This highly biomimetic permeation pattern enabled the model to distinguish high and low absorption drugs, yield a good correlation with Caco-2 permeability (R2 = 0.85). The above results indicated that the novel PPBMPA model is expected to serve as a reliable tool for rapid and reproducible drug permeability prediction.