Comparative evaluation of nephrotoxicity and antibacterial activity of free and liposomal gentamicin in rats: Biochemical, molecular and histopathological analysis

Abstract

Gentamicin is a widely used aminoglycoside antibiotic; however, its clinical use is limited by dose-dependent nephrotoxicity. Liposomal drug delivery systems may reduce toxicity while preserving antibacterial efficacy. This study aimed to comparatively evaluate the nephrotoxic and antimicrobial effects of free and liposomal gentamicin in a rat model. Rats were divided into control, free gentamicin (FGT; 100 mg/kg), and liposomal gentamicin (LipGT; 100 mg/kg) groups administered for 7 days. Renal function parameters, oxidative stress biomarkers, pro-inflammatory cytokines, renal injury markers, and gene expression levels were analyzed. Free gentamicin significantly increased serum BUN and creatinine levels, oxidative stress, inflammatory cytokines, and renal injury biomarkers. Liposomal gentamicin attenuated these alterations, demonstrating a protective effect. Creatinine levels showed partial normalization, whereas BUN exhibited a distinct response. Liposomal treatment partially restored SIRT3 expression but did not normalize PAX2. Histopathological findings supported these results. Antimicrobial analysis revealed preserved activity against Escherichia coli but reduced efficacy against Staphylococcus aureus. Liposomal encapsulation mitigates gentamicin-induced nephrotoxicity while partially maintaining antibacterial activity, suggesting a promising strategy to improve drug safety.