N‐Acetyl cysteine‐loaded liposomes to reduce iron overload‐induced toxicity in human kidney cells

BACKGROUND Iron overload in the body generates free radicals through the Fenton reaction, leading to adverse effects on various organs. Several antioxidants have been recommended to treat iron‐related diseases effectively. N ‐Acetyl cysteine (NAC), a potent antioxidant, was investigated in this study for its potential to mitigate iron overload‐induced cell death. A liposomal formulation was developed to encapsulate NAC, employing the reverse phase evaporation method, to enhance its delivery and effectiveness. The liposomal NAC was characterized by evaluating its size, zeta potential, morphology and release profiles. RESULTS The protective effect of liposomal NAC against iron overload‐induced toxicity was assessed in human kidney 2 (HK‐2) cells. Cell viability assays (Cell Counting Kit 8) and reactive oxygen species assays (DCFDA assay) confirmed the effectiveness of liposomal NAC in inhibiting ferroptosis induced by slow iron uptake (1 mmol L −1 ferric ammonium citrate). Additionally, liposomal NAC protected cells from toxicity resulting from rapid iron uptake (50 μmol L −1 ferric ammonium citrate, 20 μmol L −1 8‐hydroxyquinoline). The liposomal formulation demonstrated an enhanced protective effect compared to free NAC. CONCLUSION These findings suggest that liposomal NAC more effectively protects human kidney cells from toxicity caused by different iron uptake models than free NAC, highlighting its potential as a superior treatment option for iron overload‐induced cellular damage.