Orally engineered liver-targeted garlic exosome-like nanovesicles for astaxanthin precise delivery against alcoholic liver disease in mice.

Orally targeted strategy of nutrients has attracted obvious attention for reducing side effects and enhancing the intervention efficiency of alcoholic liver disease (ALD). Herein, novel lactobionic acid-modified garlic exosome-like nanovesicles (LA-GELN) were designed to precise delivery astaxanthin (AXT) against alcohol-induced lipid metabolism disorders. The targeted modification of nanovesicles enhanced the encapsulation efficiency of AXT (80.03%). Meanwhile, the encapsulation strategy also improved the solubility and gastrointestinal stability of AXT. In the HepG2 cell model, LA-GELN-AXT demonstrated excellent cellular uptake capacity (Pearson correlation coefficient of 0.87) and effectively alleviated oxidative stress and lipid droplet formation. In vivo studies also demonstrated that 8 h after oral administration, the hepatic fluorescence intensity in the LA-GELN and GELN groups was 1.98-fold and 1.26-fold that of the Nile red group, respectively. In the ALD mouse model, LA-GELN-AXT effectively mitigated oxidative damage, reduced inflammatory cytokine levels, restored mitochondrial function, and further alleviated lipid accumulation. Its mechanism of action was associated with the modulation of the TLR4/MyD88/NF-κB inflammatory signaling pathway and the subsequent alleviation of ALD-induced hepatic metabolic disorders.