Work

Reactive oxygen species-responsive liver-targeting nanoparticles enhance the therapeutic effect of baicalin magnesium in metabolic dysfunction-associated fatty liver disease

Year: 2025

Type: article

Abstract: • Baicalin magnesiu, which has better water solubility than baicalin, was obtained from Scutellaria baicalensis Georgi. • Baicalin magnesium can treat metabolic dysfunction-associated fatty liver disease through multiple mechanisms, including lipid-lowering, anti-inflammatory, and antioxidant effects. • Liver-targeted nanoparticles achieve precise liver drug delivery, with responsive drug release in high-ROS inflammation, ensuring lesion accumulation and reducing normal tissue effects. • The polymer synthesized in this study shows ROS responsiveness, depleting excess ROS for synergistic therapy. The interplay between lipid buildup, oxidative stress, and inflammatory responses is the key mechanism underlying metabolic dysfunction-associated fatty liver disease (MAFLD). We previously discovered that baicalin magnesium (BA-Mg), the natural form of baicalin in Scutellaria baicalensis Georgi, can alleviate liver damage through lipid-lowering, antioxidation, and anti-inflammatory effects. However, its hepatic distribution after injection is suboptimal. Therefore, we aimed to increase the hepatic BA-Mg content and thereby enhance its therapeutic effect. In this study, Gal-PEG 10K -TK-PCL 15K polymer was prepared as a carrier and the compound emulsion solvent evaporation method was adopted to generate Gal-PEG 10K -TK-PCL 15K @BA-Mg ROS-responsive liver inflammation-targeted nanoparticles. The formulation and preparation process were optimized through single-factor analysis and Box-Behnken design; structural characterization, assessment of stability and reactive oxygen species (ROS) sensitivity, and pharmacodynamic evaluation were also carried out. These nanoparticles showed 151.4 ± 1.48 nm size, 92.25 ± 0.40 % encapsulation efficiency (EE), and 26.55 ± 0.48 % drug loading capacity (DL). The nanoparticle emulsion demonstrated good stability at 4°C and an excellent ROS response under 1 mM H 2 O 2 . This preparation could significantly alleviate liver inflammation, oxidative stress, and lipid deposition in MAFLD mice, and its therapeutic effect was superior to that of BA-Mg. Overall, Gal-PEG 10K -TK-PCL 15K @BA-Mg ROS-responsive liver-targeted nanoparticles could increase the liver concentration of BA-Mg, thereby enhancing its therapeutic effect on MAFLD.

Source: International Journal of Pharmaceutics

DOI: 10.1016/j.ijpharm.2025.126354