Oral dual-targeted nanosystem for ameliorating colonic barrier injury and secondary liver injury

This study designed an oral colon-localized nanomotor system, MS@LA-BBR-(TA/CHI)₅, that achieved passive hepatic accumulation. The system employs aminated mesoporous silica conjugated with L-arginine, loaded with berberine hydrochloride (BBR), and a protective shell constructed via layer-by-layer self-assembly of tannic acid and chitosan. In vitro release studies demonstrated that the nanoformulation exhibited pH-dependent release behavior, and further accelerated drug release in the presence of 3% H₂O₂, confirming the ROS-responsive degradation. Meanwhile, the experimental results of ROS consumption and particle size variation under hydrogen peroxide conditions, further verified the ROS-responsive degradation. In animal experiments, pharmacokinetic results demonstrated that, compared with free BBR, the nanoformulation increased AUC₀-₂₄ h and Cmax by 45.0% and 70.0%, respectively, and shortened the mean absorption time by 30.2%, significantly improving oral bioavailability. In the DSS-induced colitis with liver injury mouse model, the nanomotor system adhered to inflamed colonic sites, penetrated the intestinal barrier, and accumulated in the liver. Notably, FITC-dextran permeability assay confirmed that the nanoformulation effectively restored intestinal barrier function. The results of Oil Red O staining revealed that nanoformulation groups significantly reduced hepatic lipid accumulation, furthermore, serum AST and ALT levels were significantly decreased in the nanoformulation groups compared with the DSS model groups (p < 0.05). Collectively, the nanosystem effectively alleviated colonic barrier injury and hepatic steatosis, offering a promising therapeutic strategy for colitis and secondary liver injury.