Lipid-Based Formulations Reveal a Bioaccessibility-Permeability Mismatch in Lipophilic Functional Food Bioactives.

This study evaluated how lipid-based food formulations affect sequential determinants of predicted intestinal absorption using silybin from milk thistle and vitamin A from moringa extract as model lipophilic compounds. Milk thistle powder, an excipient-based milk thistle formulation, and the excipient-based milk thistle formulation combined with piperine or MK-571 were subjected to in vitro digestion and Caco-2 transport assays. Moringa extract, powder-based lecithin liposomes, and liquid-based lecithin liposomes were evaluated for vitamin A dissolution, retinyl acetate-to-retinol conversion, digestive recovery, and epithelial transport. The excipient-based milk thistle formulation had only a minor effect on silybin digestive recovery (approximately 13.9%-16.0%) but increased silybin apparent permeability from approximately 1.3 × 10-6 cm/s for milk thistle powder to approximately 3.6 × 10-6 cm/s for the excipient-based formulation. Piperine reduced the efflux ratio of silybin in the direct transport model, but this effect was not retained after digestion. In contrast, powder-based moringa liposomes markedly increased predigestion vitamin A dissolution (70.86% of the initial amount) and total vitamin A digestive recovery (47.81%), but did not produce the highest short-term basolateral transport. These findings suggest that lipid-based food formulations can shift the apparent rate-limiting step of predicted intestinal absorption in a compound- and matrix-dependent manner. PRACTICAL APPLICATIONS: This study provides a practical framework for developing functional foods containing poorly soluble bioactives. Sequential digestion and Caco-2 transport testing can help food companies select formulations based on the apparent rate-limiting step of each bioactive ingredient.