Encapsulation of oxyresveratrol in natural polymer coated zein nanocomplex: Preparation, characterization, stability, in vitro digestion, and biological activity

Oxyresveratrol (OXY), a plant-derived polyphenol, exhibits promising bioactivities but encounters practical constraints owing to its poor water solubility and instability. To address these challenges, OXY-loaded nanocomplexes were fabricated via the antisolvent precipitation method using zein, sodium caseinate (SC), and sodium alginate (SA) as a delivery matrix. The optimized OXY-zein/SC/SA complexes possessed a median size centered at 220 nm, a surface potential of −32 mV, an encapsulation efficiency of 83.86 %, and a loading capacity of 9.45 %. Morphological observation (using Scanning Electron Microscopy and Transmission Electron Microscopy) confirmed the formation of a spherical core-shell structure. Evidence for the strategic construction of the complex framework was provided by a convergence of Fourier Transform-Infrared spectroscopy, X-ray Diffraction, and Nuclear Magnetic Resonance spectroscopy data. Thermogravimetric and Derivative Thermogravimetry profiles showed higher decomposition temperatures, confirming enhanced stability from the structural design. Molecular dynamics simulations revealed that stable binding between OXY-zein and SC was primarily driven by hydrogen bonding and surface complementarity, while SA modulated the microenvironment through structural rearrangement and steric shielding. Kinetic modeling indicated that the incorporation of SC and SA shifted the release behavior from Fickian diffusion to a complex mechanism governed by matrix erosion and structural relaxation. The stable nanocomplexes outperformed native OXY in radical scavenging capacity while also maintaining excellent biocompatibility with Caco-2 cells and high tolerance to fluctuations in salinity and pH. These findings elucidate the formation mechanisms of the OXY-zein/SC/SA system, establishing a theoretical framework for the delivery of hydrophobic polyphenols in functional foods and nutraceuticals.