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. In vivo, 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.
Luo et al. (Wed,) studied this question.