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

Abstract

(1) Background: Drug-induced liver injury 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 dis-ease treatments due to their capacity to enhance drug solubility, provide drug protection, and prolong release duration, thereby improving drug bioavailability and increasing therapeutic efficacy. We initially present a nanostructured carrier incorporating glycyrrhetinic acid and transferrin. The ex-periments prove that this carrier can achieve the targeted and prolonged delivery of hepatocyte growth factor; (2) Methods: Hepatocyte growth factor was loaded to the nanocarrier successfully with hepatocyte growth factor modified glycyr-rhetinic acid by ultrasound techniques, and subsequently characterized by parti-cle size, zeta potential, drug loading capacity and encapsulation efficiency, morphology and release kinetics in vitro. 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 ra-tio was determined to be 42.47 %. In vitro studies demonstrated that the nano-particles released hepatocyte growth factor continuously, thereby prolonging the action time and effectively protecting liver injury cell models from drug-induced hepatotoxicity. For the two kinds of drug-induced liver injury cell mod-els, the capacity of the drug-carrying nanoparticles to enhance cellular prolifera-tion was superior to that of hepatocyte growth factor, magnesium isoglycyrrhizi-nate 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, indi-cating the targeted effect mediated by the drug-carrying nanoparticles. The re-sults of flow cytometry, apoptosis, biochemical indexes and cytotoxicity tests exhibited consistency. (4) Conclusions: The drug-carrying nanoparticles exhibits potential as a thera-peutic agent with heptoprotective properties.