This study focuses on the development and evaluation of glycyrrhetinic acid (GA)-modified thiolated nanocarriers for targeted delivery of 5-fluorouracil (5-FU) in hepatocellular carcinoma (HCC). The nanocarrier system integrates thiolated chitosan and thiolated Eudragit, both chemically conjugated with GA to exploit its natural affinity for hepatocytes. The synthesis of thiolated polymers was achieved via carbodiimide-mediated coupling between primary amino groups of chitosan/Eudragit and carboxyl groups of thioglycolic acid, followed by lyophilization to yield stable, water-soluble conjugates. Nanoparticles were prepared using a solvent diffusion method combined with high-pressure homogenization and probe sonication, ensuring optimal size control and uniform dispersion. Characterization techniques including FTIR, XRD, DLS, SEM, and AFM confirmed successful formation of the nanocomposite. FTIR spectra displayed characteristic peaks at 2333 cm⁻¹ (S-H stretch), 882 cm⁻¹ (S-S bond), and 1733 cm⁻¹ (C=O), confirming thiolation. XRD patterns showed a shift from sharp crystalline peaks to broad amorphous halos after drug loading, indicating disruption of crystal lattice and effective drug entrapment. Particle size analysis revealed mean diameters of 593 nm (blank) and 628.4 nm (drug-loaded), with PDI values below 0.3, suggesting excellent colloidal stability.
In vitro cytotoxicity was assessed using HepG2 cells via MTT assay, demonstrating dose-dependent inhibition of cell viability.137234-62-9 medchemexpress The IC₅₀ value of the GA-modified nanocarrier was determined to be 333.1 µg/mL, significantly lower than that of free 5-FU, indicating enhanced therapeutic potency. Confocal microscopy and flow cytometry further revealed increased cellular uptake of the nanocomposite compared to non-targeted controls, confirming active targeting via GA-mediated receptor recognition. In vivo studies were conducted in Wistar rats induced with HCC through diethylnitrosamine (DEN) and carbon tetrachloride (CCl₄).LCK Antibody custom synthesis After treatment with varying doses of the 5-FU-loaded nanocarrier, significant reductions in serum liver enzymes—SGOT, SGPT, ALP, GGT, and total bilirubin—were observed, with dose-dependent improvement in hepatic function.PMID:34863007 Histopathological analysis revealed marked reversal of tumor burden, including reduced nodule formation, normalized lobular architecture, decreased necrosis, and diminished inflammatory infiltrates in treated animals. HPLC analysis of liver homogenates confirmed substantial accumulation of 5-FU in hepatic tissue, particularly in the high-dose group, validating effective liver targeting. Molecular docking results demonstrated strong binding interactions between GA and LRH-1 (G-score: -7.65 kcal/mol), as well as between thiolated Eudragit and LRH-1 (G-score: -9.1 kcal/mol), suggesting dual mechanisms of action involving both drug delivery and pathway modulation. These findings highlight the potential of GA-reinforced thiolated nanocarriers as a multifunctional platform for HCC therapy, combining targeted delivery, enhanced bioavailability, and intrinsic antitumor activity.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
