Abstract
Background/Objectives: Gallic acid (GA) is a dietary phenolic acid with antioxidant and anti-inflammatory activity, but its poor stability may limit its health-promoting benefits. Plant-derived extracellular vesicles (EVs) are naturally occurring nanostructures that have emerged as potential carriers for dietary bioactive compounds. However, whether tissue origin affects their capacity to load GA and functional performance remains unclear. Methods: Exosome-like nanoparticles (ELNs) with characteristics similar to EVs were isolated from grape skin (GS) and grape pulp (GP) by differential ultracentrifugation and loaded with GA using ultrasound-assisted technology. GA loading efficiency and stability under thermal, ultraviolet (UV), and simulated gastrointestinal conditions were evaluated. The protective effects of GA-loaded ELNs against oxidative stress and inflammatory damage were assessed in RAW264.7 macrophages. Results: At an ELN protein-to-GA mass ratio of 2:1, GS ELNs exhibited a higher GA loading efficiency than GP ELNs (86.06 ± 2.23% vs. 5.25 ± 2.93%) and achieved a GA loading content of 1721.28 ± 44.50 µg/mg. This difference may be associated with the lipid composition of ELNs. Compared with free GA, GA-loaded ELNs exhibited greater stability under thermal, UV, and simulated gastrointestinal conditions. In addition, GA-loaded ELNs also provided protection against oxidative stress and inflammatory damage in RAW264.7 cells. Conclusions: These results provide preliminary evidence that tissue origin influences the functional properties of ELNs, including their loading capacity and ability to enhance the stability of bioactive compounds. In addition, GA-loaded ELNs exhibit antioxidant and anti-inflammatory activities, suggesting their potential nutritional and health benefits.