Development of a Novel Pharmaceutical Formula of Nanoparticle Lipid Carriers of Gentamicin/α-Tocopherol and In Vivo Assessment of the Antioxidant Protective Effect of α-Tocopherol in Gentamicin-Induced Nephrotoxicity

Abstract

Gentamicin is a potent antibiotic with a nephrotoxicity drawback which limits its use. D-α-tocopherol polyethylene glycol succinate (α-tocopherol) is widely used as a surfactant and have potent antioxidant properties. This study aimed to assess the protective effect of α-tocopherol on gentamicin-induced nephrotoxicity by loading gentamicin on nanostructured lipid carriers (NLC). In vivo, the product was administered intravenously to three groups of rabbits (control, gentamicin and gentamicin/α-tocopherol NLC) for 10 consecutive days. Blood was collected on days 1, 5 and 10 to assess renal function. A significant difference in all plasma parameters related to kidney function were observed in the gentamicin group compared to the control by day 5 and 10, confirming the nephrotoxicity effect. On the other hand, the same parameter levels of the NLC group were significantly different compared to the gentamicin group, confirming the protective effect on kidney function. Gentamicin also caused significant decreases in plasma levels of glutathione sulfhydryl (GSH) and superoxide dismutase (SOD) activity. However, gentamicin-α-tocopherol NLC significantly elevates both plasma levels of GSH as well as SOD activity. The present work indicates that, loading of gentamicin on NLC by using α-tocopherol, is an innovative strategy to protect against aminoglycoside-induced nephrotoxicity due to its antioxidant activity.