Enhanced resistance to drug-induced liver injury using glycyrrhetinic acid modified-transferrin nanoparticles loading hepatocyte growth factor

(1) Background: drug-induced liver injury (DILI) is a prevalent global health concern that necessitates urgent development of safe and effective treatment options for patients. Drug-carrying nanoparticles have garnered significant attention for disease treatments due to their capacity to enhance drug solubility, provide drug protection, and prolong release duration, thereby improving drug bioavailability and increasing therapeutic efficacy. In this study, we initially present a nanostructured carrier incorporating glycyrrhetinic acid and transferrin. The experiments prove that this carrier can achieve the targeted and prolonged delivery of hepatocyte growth factor (HGF); (2) Methods: HGF was loaded to the nanocarrier successfully with HGF modified glycyrrhetinic acid by ultrasound techniques, and subsequently characterized by particle size, zeta potential, drug loading capacity and encapsulation efficiency, morphology and release kinetics<i>in vitro</i>. The hepatoprotective effects were evaluated by cell proliferation, cellular uptake, apoptosis, ALT and AST levels in three-dimensional spherical liver injury cell models induced by paracetamol and rifampicin; (3) Results: the drug-carrying nanoparticles were synthesized successfully with favorable nanoparticle characteristics. The optimal dosage ratio was determined to be 42.47%.<i>In vitro</i>studies demonstrated that the nanoparticles released HGF continuously, thereby prolonging the action time and effectively protecting liver injury cell models from drug-induced hepatotoxicity. For the two kinds of DILI cell models, the capacity of the drug-carrying nanoparticles to enhance cellular proliferation was superior to that of HGF, magnesium isoglycyrrhizinate and their physical mixture. The results of cell uptake experiments showed that HepG2/C3A cells had a high uptake rate of the drug-carrying nanoparticles, especially evidenced by the enhanced fluorescence signal in the nucleus, indicating the targeted effect mediated by the drug-carrying nanoparticles. The results of flow cytometry, apoptosis, biochemical indexes and cytotoxicity tests exhibited consistency. All in all, the drug-carrying nanoparticles demonstrated a stronger protective effect; (4) Conclusions: the drug-carrying nanoparticles exhibits potential as a therapeutic agent with heptoprotective properties.