Enhancing Intestinal Permeability of Theaflavin-3,3'-digallate by Chitosan-Caseinophosphopeptides Nanocomplexes

Low intestinal permeability is an unfavorable feature that limits the bioavailability of many hydrophilic polyphenols. In this study, chitosan (CS) was used to complex with caseinophosphopeptides (CPPs), aiming to improve the intestinal permeability of theaflavin-3,3'-digallate (TF-3), a characteristic polyphenol in black tea with poor intestinal permeability. Complexation between CS and CPPs was systemically investigated by turbidimetric titration under various conditions, revealing that electrostatic interaction was the dominant force. The sizes, PDIs, and ζ potentials of CS-CPP nanocomplexes varied with their compositions. The optimized CS-CPP nanocomplex was subsequently used to encapsulate TF-3, which showed high encapsulation efficiency and low cytotoxicity. Microstructural studies showed strong intermolecular associations between CS, CPPs, and TF-3. Encapsulation of TF-3 maintained the globular unit structure of CS-CPP nanocomplexes, but high concentrations of TF-3 resulted in aggregation. Importantly, as proved using the Caco-2 monolayer model, the intestinal permeability of TF-3 was significantly enhanced by the CS-CPP nanocomplexes.