Abstract
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.