Radioprotection and enhanced efficacy by curcumin-loaded chitosan nanoparticles in mitigating radiation-induced liver injury

Abstract

Introduction: This study aimed to evaluate the protective effect of curcumin-loaded chitosan nanoparticles (CurCsNPs) against radiation-induced liver damage in rats. Curcumin's antioxidant and anti-inflammatory properties, combined with chitosan's drug delivery potential, were leveraged to mitigate the harmful effects of ionizing radiation (IR) on the liver. Methods: Cur-CsNPs were characterized using TEM, XRD, DLS, and FTIR. Spectrophotometry assessed drug loading and curcumin release. Cytotoxicity was evaluated using MTT assay on HepG2 cells. The experimental design involved eight groups: a control group, three groups receiving different doses of Cur-CsNPs (25, 50, 100 mg/kg), three groups receiving the same doses plus irradiation (6Gy), and one group receiving irradiation only. H&E and MTC staining were used for histopathological evaluation. The activity of liver enzymes ALT, AST, ALP, and GGT was measured. Results: In this study, three types of Cur-CsNPs were synthesized using varying ratios of chitosan to TPP ratios, resulting in average sizes of 660 nm, 230 nm, and 120 nm. Cur-CsNPs which exhibited the highest encapsulation efficiency, was selected for further evaluation. TEM confirmed its spherical shape with an average size of 37 nm. Drug release studies demonstrated an 85 release at pH 5.4 within 70 h. MTT assays indicated low cytotoxicity, with high cell viability maintained across all concentrations and time points. Liver enzyme analysis in rats revealed that Cur-CsNPs, particularly when combined with radiation, mitigated radiation-induced liver damage. Histological examination showed that treatment with Cur-CsNPs reduced liver damage, inflammation, necrosis, and fibrosis in irradiated groups compared to the radiation-only group, which exhibited severe liver damage. Conclusion: The findings of this study show that Cur-CsNPs possess significant potential as a therapeutic agent for protecting against radiation-induced liver injury. The favorable drug release profile, low cytotoxicity, and protective effects observed in enzyme levels and histological assessments highlight the efficacy of Cur-CsNPs. The findings imply that Cur-CsNPs could be an effective strategy for enhancing liver protection in radiation exposure scenarios, warranting further investigation into their mechanisms of action and potential clinical applications.