Liver-targeted glycyrrhetinic acid-cyclodextrin-pullulan nanoparticles for drug delivery in the treatment of liver fibrosis.

In this study, we developed liver-targeted glycyrrhetinic acid-cyclodextrin-pullulan nanoparticles (GCDPu NPs) loaded with the hepatoprotective agent glycyrrhetinic acid (GA/GCDPu NPs) to enhance the prevention of liver fibrosis. The GCDPu NPs were characterized using differential scanning calorimetry (DSC). Spherical GA/GCDPu NPs were fabricated via dynamic dialysis, demonstrating high encapsulation efficiency and drug loading capacity. In vitro evaluations revealed that GA/GCDPu NPs exhibited negligible hemolytic activity and organ toxicity. Moreover, the release profile of GA from the nanoparticles was slow and sustained compared to free GA. This formulation significantly improved drug bioavailability, prolonged systemic circulation time and reduced clearance rates. Tissue distribution and in vivo mouse imaging studies confirmed the liver-targeting efficacy of GA/GCDPu NPs. A murine model of liver fibrosis was established, and treatment with GA/GCDPu NPs effectively mitigated disease progression and markedly alleviated liver injury. Therefore, utilizing GCDPu as a liver-targeted delivery system for therapeutic agents represents a promising strategy for the management of liver fibrosis.