A hepatocyte targeted silymarin sea cucumber peptide-galactose nanoparticle for the alleviation of ethanol-induced damage in cells.

Alcoholic liver disease (ALD) poses a significant global health challenge, and the development of effective therapeutic approaches could greatly improve health outcomes and increase life expectancy. Silymarin, a natural flavonolignan compound, has well-documented hepatoprotective properties in both in vitro and in vivo studies. However, its clinical use is limited because of poor water solubility and low bioavailability. We herein designed and characterized a novel hepatocyte-targeted delivery system for silymarin using a sea cucumber peptide (SCP)-galactose (Gal) Maillard conjugate. The resulting silymarin-loaded SCP-Gal nanocarrier (silymarin@SCP-Gal) measured 42.28 nm in diameter, exhibited a uniform spherical morphology, demonstrated high stability, and showed favorable biocompatibility. The encapsulation efficiency (75.54 ± 4.71) %, and the drug loading rate was (6.29 ± 2.56)%. Importantly, silymarin@SCP-Gal accumulated efficiently in LO2 cells and was retained for extended periods, an effect attributed to the galactosyl component of the carrier. This formulation significantly reduced ethanol-induced cytotoxicity and oxidative stress in hepatocytes. Overall, silymarin@SCP-Gal provided an innovative and effective platform for delivering hydrophobic bioactive compound of silymarin to hepatocytes. By improving solubility, enhancing bioavailability, and strengthening cellular protection against ethanol-induced injury, this nanoparticle system demonstrated considerable potential for therapeutic intervention in ALD.