Morin-loaded water-soluble nanomicelles as a novel anti-alcohol intoxication medication

Acute alcohol intoxication (AAI) poses serious health risks. Currently, no approved therapy effectively treats both CNS depression and tissue damage in AAI. Standard care, including supportive measures and off-label naloxone, manages respiratory depression but fails to prevent oxidative organ injury. We identified morin (MOR) as a promising candidate for addressing these challenges. Given that MOR is limited by poor water solubility and low oral bioavailability, we developed water-soluble nano-micelle formulations (MOR-Ms) using Kolliphor HS15 (HS15) as a surfactant for intravenous administration. The resulting MOR-Ms exhibited a uniform size of 13.84 ± 0.23 nm and a zeta potential of -9.99 ± 0.21 mV. <i>In vivo</i>, MOR-Ms accelerated alcohol metabolism by enhancing hepatic enzyme activity. In an AAI mouse model induced by intraperitoneal injection of 50% alcohol (10 ml/kg), MOR-Ms (3 mg/kg) significantly shortened the duration of loss of righting reflex (LORR) by 58.01%, which was comparable to the 67.83% reduction achieved by naloxone (1 mg/kg). Furthermore, MOR-Ms markedly lessened tissue damage by decreasing malondialdehyde (MDA) levels (by 32.01% in liver and 53.75% in brain compared to the model group) and boosting antioxidant enzyme activity. These results highlight the potential of MOR-Ms as a promising therapeutic approach for AAI.