Evaluation of a bismuth-ellagic acid metal-organic framework for the prophylaxis of inflammatory disorders

Ellagic acid (EA) is a potent antioxidant limited by poor gastrointestinal stability. SU-101 is an EA-bismuth metal-organic framework (MOF), and whether it acts systemically after oral dosing is unknown. We evaluated the prophylactic efficacy and organ distribution of oral SU-101 in systemic and localized inflammatory models.

SU-101 was tested in simulated gastrointestinal fluids, and its radical-scavenging activity was compared with that of free EA. In mice with LPS/D-galactosamine-induced acute liver injury (ALI), oral SU-101 was given prophylactically; in a PMA-induced ear edema model, SU-101 was administered locally after challenge. Tissue bismuth was quantified by ICP-MS with naive controls.

SU-101 retained its framework and antioxidant activity after simulated digestion. In ALI, SU-101 dose-dependently reduced transaminases, IL-6, TNF-α, and MDA, restored SOD, CAT, and GSH, and suppressed hepatic iNOS and COX-2, exceeding N-acetylcysteine (NAC). In the ear model, SU-101 dose-dependently attenuated swelling, oxidative stress, and cytokines. Bismuth predominantly accumulated in the liver, followed by the kidneys.

Oral SU-101 is a liver-enriched nanoplatform that confers prophylactic hepatoprotection superior to NAC in systemic ALI and attenuates local inflammation in the ear model, supporting the drug-as-ligand MOF strategy for empowering natural antioxidants.