Oral alginate microspheres deliver Rg3/aspirin liposomes to modulate foam cells and gut microbiota in atherosclerosis.

mice, integrated 16 S rRNA sequencing and untargeted metabolomics revealed that RALM reshaped HFD-induced dysbiosis and modulated the metabolic profile, characterized by an increased Bacteroidetes/Firmicutes (B/F) ratio along with decreased prostaglandin E2 (PGE2) and elevated arginine levels. Fluorescence tracking experiment further demonstrated that the liberated RA-Lipo accumulated within aortic plaques. At the cellular level, RA-Lipo activated the PPARγ pathway, thereby enhancing cholesterol efflux and inhibiting foam cell formation. Ultimately, this synergistic regulation translated into remarkable therapeutic efficacy, effectively reducing plaque burden, suppressing pro-inflammatory cytokines, and demonstrating superior anticoagulant activity. Supported by a favorable safety evaluation, this RALM platform offers a comprehensive approach for alleviating atherosclerosis progression.