Walnut Protein Peptide Nanoparticles with Protective Mineralization: Resveratrol Encapsulation, Intestinal-Targeted Delivery and Synergistic Antioxidant Activity

Resveratrol (RES) suffers from low bioavailability and poor gastrointestinal stability, limiting its health benefits. To overcome these challenges, we developed biomimetic mineralized nanoparticles based on walnut protein peptides (WPP-RES@CaP) for intestinal-targeted RES delivery. WPP with a 31.83% degree of hydrolysis was optimal for RES encapsulation. Subsequent mineralization with 5 mM Ca²⁺ significantly enhanced the encapsulation efficiency (EE) to 95.86%, compared to 73.69% for non-mineralized WPP-RES nanoparticles. The particle size and zeta potential of WPP-RES@CaP were 795 ± 16 nm and -27 ± 1 mV, respectively. Beyond the initial hydrophobic and π-π interactions, mineralization introduced additional stabilizing forces, including metal-ligand coordination, salt bridges, and electrostatic interactions, which collectively enhanced the structural integrity and RES retention of WPP-RES@CaP. During in vitro gastrointestinal digestion, the formation of a CaP shell protected RES and WPP from excessive degradation in the gastric phase. The 77.57% RES in WPP-RES@CaP was continuously released in the intestinal phase, which was higher than that of WPP-RES (49.73%). Meanwhile, the introduction of Ca²⁺ promoted the antioxidant activity of WPP-RES@CaP, which demonstrated higher DPPH and ABTS radical-scavenging activity assays than WPP-RES both before and after digestion. It was probably due to the synergistic effect of more released RES, antioxidant-free amino acids, and peptides. This mineralized peptide-based system provided a strategy for improving the delivery of hydrophobic bioactive compounds in functional foods.