Fabrication and Characterization of Zein/Sodium Alginate Nanoparticles Loaded with Oxyresveratrol: Formation Mechanism, Molecular Dynamics Insights, and In Vitro Antioxidant Capacity

Oxyresveratrol (Oxy) exhibits a diverse range of biological activities. However, its practical application is constrained by low aqueous solubility and chemical instability. In this work, Oxy-loaded zein (Z) nanoparticles (NPs) stabilized by a sodium alginate (Alg) coating (Oxy-Z/Alg NPs) were fabricated using an antisolvent precipitation method. The absence of crystalline peaks in X-ray diffraction analysis suggested that Oxy was dispersed as an amorphous phase in NPs, while the Fourier transform infrared spectra identified strong interfacial associations between the components. The stabilization of the NPs is attributed to the site-specific binding of Oxy with Z's SER-162 and GLN-174 residues. Molecular docking, molecular dynamics simulations, and differential scanning calorimetry profiles evidenced the formation of intermolecular hydrogen bonds. Dynamic light scattering analysis showed that the nanocomplexes had a nano-scale dimension (243 ± 6 nm) and a zeta potential of -36 mV. SEM micrographs revealed that the NPs possessed a spherical morphology. The NPs exhibited colloidal stability against prolonged heating (80 °C for 75 min), ionic strengths (up to 100 mM NaCl), and pH range (2.0-10.0). Encapsulation within the Alg coating enhanced Oxy's antioxidant capacity over its unprotected form by shielding its core bioactivity from degradation. The Oxy-Z/Alg nano-system shows significant promise for the encapsulation of Oxy, providing a practical basis for its integration into nutraceuticals and functional food fields.