From poor solubility to precision delivery: Zein–κ-carrageenan nanovehicles unlock dihydromyricetin's bioactive potential

Dihydromyricetin (DMY) possesses potent antioxidant, anti-inflammatory and neuroprotective activities, yet its potential applications are curtailed by extremely low aqueous solubility and limited bioaccessibility. To overcome these constraints, the Zein-DMY/κ-carrageenan (κ-CGN) nanoparticles were engineered via anti-solvent precipitation at pH 5 (zein:κ-CGN mass ratio of 6:4) that reached 83.1% encapsulation efficiency. Multispectral analysis (FTIR, fluorescence, XRD) combined with molecular docking showed that hydrogen bonding, electrostatic and hydrophobic interactions were the main driving forces for the formation of nanoparticles, and DMY was anchored in the hydrophobic region of Zein. The dense sulfate groups of κ-CGN electrostatically stabilized the surface of nanoparticles, preventing their aggregation. Compared with free DMY, the nanocomposite retained strong antioxidant activity (95.25% for DPPH and 97.20% for ABTS), increased water solubility 4.88-fold (3.12 ± 0.07 mg/mL) and enhanced bioaccessibility 1.65-fold (37.31%). In vitro digestion simulations, coupled with SEM and release kinetics modeling, demonstrated the controlled release characteristics of nanoparticles in intestinal fluid. The release kinetics closely adhered to the Ritger-Peppas model, indicating Fickian diffusion behavior. This scalable, food-grade nanocarrier offers a robust strategy to enhance the solubility, bioaccessibility and targeted intestinal delivery of DMY for functional foods and nutraceuticals.