Homologous ginger-derived vesicle-like nanocarriers enhance the stability, gastrointestinal bioaccessibility, and macrophage anti-inflammatory activity of 6-gingerol.

The application of 6-gingerol (6-G) in functional foods is limited by its poor aqueous dispersibility, chemical instability, and low oral bioaccessibility. Herein, ginger-derived extracellular vesicle-like nanovesicles (GDEVs) were developed as homologous vesicular matrices for stabilizing and delivering 6-G. GDEVs-6-G was prepared using an ultrasonication-assisted method and exhibited high encapsulation efficiency (87.04%) and loading capacity (11.81%). Structural characterization showed that 6-G was incorporated into GDEVs mainly through non-covalent interactions without disrupting vesicle morphology. Compared with free 6-G, GDEVs-6-G showed improved resistance to heat, UV irradiation, pH variation, ionic strength, and storage at -80 °C, indicating enhanced processing and storage stability. During simulated gastrointestinal digestion, GDEVs-6-G showed a sustained release profile and increased the bioaccessibility of 6-G from 26.23% to 43.34%. In LPS-stimulated RAW264.7 macrophages, GDEVs-6-G exhibited good cytocompatibility, promoted cellular uptake, reduced intracellular ROS accumulation, and more effectively suppressed NO production and the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, than free 6-G or blank GDEVs. These results demonstrate that GDEVs can act as homologous food-derived vesicular carriers to enhance the stability, gastrointestinal bioaccessibility, and macrophage-level antioxidant and anti-inflammatory functions of 6-G.