Eradication of methicillin-resistant Staphylococcus aureus infection by nanoliposomes loaded with gentamicin and oleic acid

Abstract

Context: Methicillin-resistant Staphylococcus aureus (MRSA) infection with its high incidence is responsible for nosocomial infections. MRSA strains resistant to multiple antibiotics have emerged increasingly. Recently, combination therapy and efficient drug delivery systems are developed to treat infections.Objective: The aim of the present study was to evaluate antibacterial activities of combination of oleic acid and gentamicin against MRSA, in both free and liposomal forms, and in comparison with vancomycin.Materials and methods: The antibacterial activities against MRSA ATCC 43300 were assessed by the determination of minimum inhibitory concentration (MIC), MBC, and Fractional Inhibitory Concentration Index (FICI). The time-kill assays were performed to evaluate the potency of antibacterial agents. Nanoliposomal formulations of gentamicin, oleic acid, and combination of gentamicin with oleic acid were prepared by the dehydration–rehydration (DRV) method and characterized for size, zeta potential, and encapsulation efficiency.Results: MIC values of gentamicin and oleic acid were 19.5 and >250 µg/ml, respectively. Synergetic effects were observed by the gentamicin and oleic acid combination; FICI was 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 15- and 27-fold, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective formula in time-kill study.Discussion and conclusion: Liposomal formulation showed a higher antibacterial activity in comparison with the free forms and vancomycin. These carriers can improve antimicrobial activity as well as reducing the effective concentration required and inducing rapid bacterial clearance.