Synergistic effect of vancomycin and interferon-gamma-loaded chitosan nanogels on TNF-α gene expression in methicillin-resistant Staphylococcus aureus (MRSA) -infected mice

Increasing antibiotic resistance of Staphylococcus aureus has led to attempts to discover new antimicrobial agents, including the use of nanoparticles. The aim of this study was to synthesize vanosomycin and interferon gamma (IFN-γ) loaded chitosan nanogels and to evaluate the expression of TNF-α gene in mice infected with methicillin-resistant Staphylococcus aureus (MRSA). After synthesis and confirmation of chitosan nanogels, loading of vancomycin and IFN-γ in these nanogels was performed and confirmed by FTIR analysis. Then the antibacterial activity of nanogels was evaluated. At pHs of 6.5 and 7.4, the minimum inhibitory concentration (MIC) for vancomycin-loaded nanogels was 8 and 64 µg/ml, respectively. The MIC was calculated to be 1024 µg/ml for chitosan nanogels and IFN-γ-loaded nanogels and 1 µg/ml for free vancomycin. Then 48 mice were divided into 6 groups: control, MRSA, nanogels, drug nanogels, IFN-γ nanogels and nanogels (drug and IFN-γ). After infecting the groups (except control) with MRSA, 100 mg/kg of nanogels, drug nanogels, IFN-γ nanogels and nanogels (drug and IFN-γ) were added to groups 3 to 6, respectively. Finally, at 6, 12 and 24 hours, a number of mice from each group were anesthetized and their spleen was evaluated for TNF-α gene expression by RT-PCR. The results showed that in groups 4, 5 and 6, compared to the MRSA group, TNF-α gene expression showed a significant decrease after 24 hours. Therefore, it could be concluded that simultaneous injection of drug nanogels and IFN-γ nanogels in infected mice is much more effective than single injection of each of these nanogels.