Synergistic effect of vancomycin and gallic acid loaded MCM-41 mesoporous silica nanoparticles for septic arthritis management

Treatment of septic arthritis has become a major challenge due to the increasing frequency of antibiotic resistance developed by Staphylococcus aureus. Combination drug therapy using antibiotics and polyphenols can work in synergy to overcome the increasing multiple drug resistance (MDR). Our study design involved loading vancomycin and gallic acid into bare mesoporous silica nanoparticles (MSNs) and amino-functionalized MSNs (AP-MSNs) to determine the minimum inhibitory concentration (MIC) of the drug-loaded MSNs by agar well diffusion using Staphylococcus aureus, and the cytotoxicity was studied using NIH/3T3 fibroblast cells. The successful incorporation of vancomycin and gallic acid into the MSNs was observed by the change in the absorption frequencies of MSNs from the Fourier transform infra-red (FTIR) spectrum, and the transmission electron microscopy (TEM) results show all the MSNs have homogenous cylindrical rod like shape, and the dynamic light scattering (DLS) results show a significant change in the mean diameter of AP-MSNs (180.8 nm ± 10.33 nm) compared to bare MSNs (247.2 nm ± 11.56 nm). The results indicate that bare MSNs have negative zeta potential of −25.8 ± 0.73 mV, and the AP-MSNs have a positive zeta potential of +31.5 ± 0.88 mV, and both have increased colloidal stability. The results indicate that drug-loaded AP-MSNs show better cell viability and biocompatibility than bare MSNs (p < 0.05). Further synergistic effect of vancomycin and gallic acid loaded AP-MSNs have higher antibacterial effect showing zone size of 19.7 ± 0.66 mm compared to all other groups and the membrane integrity of the staphylococcal cells were severely affected causing severe damage to the bacterial membrane, which was confirmed by FESEM analysis. Further, there was a significant increase (p < 0.01) in the death percentage of staphylococcal cells when treated with a combination of AP-MSNs/GA and AP-MSNs/VA. The results show that the synergistic effect of gallic acid and vancomycin, when loaded into the MSNs, show promising antibacterial effects and gallic acid can act as an adjuvant with vancomycin to overcome the antibacterial resistance. Further, this drug loaded cargo can be administered by intra-articular injection as an alternative therapy for staphylococcal joint infections.

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