Layer-by-layer reinforced-mediated sustained-release nanoantioxidants for long-lasting prevention against drug-induced liver injury

Drug-induced liver injury (DILI) is a commonly encountered and diagnostically complex etiology of acute liver failure, characterized by early indications of hepatic oxidative stress. The most economical approach for DILI treatment is effective and durable oxidative stress prevention. Herein, we propose a long-lasting nanoantioxidant called PDA-Zn-BAI NPs characterized by sustained-release of baicalein (a natural antioxidant) for the long-lasting prevention of DILI. It is constructed using dopamine as an intermediate and layer-by-layer reinforcement strategy based on Zn2+-mediated coordination bonding, π-π stacking, and steric hindrance made of polydopamine network. Optimized PDA-Zn-BAI NPs performed a satisfactory sustained-release effect (36.67% ± 6.67 in normal condition and 60.32% ± 3.19 in acid condition of cumulative release within 5 days). Furthermore, it's been found that PDA-Zn-BAI NPs could continuously be accumulated in the liver with negligible hepatotoxicity and were activated to effectively scavenge reactive oxygen species to break off the damage of acetaminophen to the liver within 5 days (ALT as an indicator, > 70% prevention effect lasts for 5 days), which was vital for the long-lasting prevention of DILI. The long-lasting detoxification by PDA-Zn-BAI NPs in patients with DILI suggested a potential clinical application, especially for those patients who need prolonged administration of hepatotoxic drugs.