Preparation of a Thermosensitive Chitosan-Sea Cucumber Peptide Hydrogel and Its Alleviating Effect on Acute Alcohol-Induced Dual Liver and Brain Injury in Mice.

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)-sea cucumber peptide (SCP) hydrogel (CS-SCP gel) loaded with SCP using NaHCO3 as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS-SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS-SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS-SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation.