Predicting intestinal effective permeability of different transport mechanisms: Comparing ex vivo porcine and in vitro dialysis models

Intestinal effective permeability (Pₑff) is among the most critical parameters that determine the bioavailability of nutrients. Rats have been widely used to estimate the Pₑff of bioactive compounds. However, distinct physiological differences between rats and humans hamper accurate prediction of the Pₑff. Herein we presented an ex vivo porcine intestinal model to predict the Pₑff of two model nutrients which involve both active transport (d-glucose) and passive transport (gallic acid). The results were compared with an in vitro dialysis model which has gained increasing interest in simulating intestinal absorption. The results indicated that the ex vivo porcine model maintained the integrity of the villus epithelium and closely predicted the human Pₑff of the two compounds. The Pₑff values of d-glucose obtained from the porcine model (2.37 × 10⁻⁴ cm/s) and the dialysis model with 8000 Da dialysis membrane (2.16 × 10⁻⁴ cm/s) were comparable to that obtained from healthy volunteers, and higher than that from Caco-2 model, rat in situ and ex vivo models. The Pₑff obtained from the in vitro dialysis model was affected by the molecular weight cut-off (MWCO). Specifically, the human Pₑff was closely predicted when 8000 MWCO was selected. The Pₑff values of gallic acid were 1.70 × 10⁻⁴ cm/s for the porcine model, 1.35 × 10⁻⁴ cm/s for the dialysis model with 8000 Da MWCO, and 1.33 × 10⁻⁴ cm/s for the 1000 Da MWCO, respectively. These values were consistent with those reported in the rat in situ and Ussing chamber models, regardless of intestinal resources. Both models exhibited potential for use in intestinal permeability assessment of nutrients and can serve as a screening tool for nutrient bioavailability and absorption.