Chitosan-polypeptide nanocomplexes crosslinked by a natural crosslinker enhanced the intestinal permeability of black tea polyphenol

Abstract

The discrepancy between in vitro and in vivo bioefficacies of hydrophilic polyphenols often stems from their low intestinal permeabilities. Chitosan (CS)-based polysaccharide-polypeptide nanocomplexes are promising delivery systems for enhancing the intestinal permeability of hydrophilic polyphenols. However, these nanocomplexes are intrinsically susceptible to pH changes, which limits their applications. In this study, the nanocomplexes self-assembled by CS and caseinophosphopeptides (CPPs) were crosslinked by a natural crosslinker genipin, aiming to improve their pH stabilities. The crosslinking reaction altered not only the size, surface charge, and morphology but also the microstructures of the CS-CPPs nanocomplexes (CCNs). Compared to the non-crosslinked counterparts, genipin-crosslinked CCNs (GCCNs) showed higher stability against pH change as they were more resistant to acid-induced dissociation at gastric pH. GCCNs were further used to encapsulate theaflavin-3,3′-digallate (TF-3), an important polyhydroxylated polyphenol in black tea that has low intestinal permeability. Encapsulation of TF-3 also influenced the physicochemical features of the nanocomplexes. Notably, loading in GCCNs significantly enhanced the in vitro intestinal permeability of TF-3. This study demonstrated that GCCNs not only had high pH stability but also had the capacity to enhance the in vitro intestinal permeability of TF-3.