Synergistic anti-microbial and anti-biofilm effects of tannic acid and tetracycline co- encapsulated in mesoporous silica nanoparticles against Staphylococcus aureus

AIMS: This study aimed to develop a mesoporous silica nanoparticle (MSN)-based dual-drug delivery system co-encapsulating tannic acid (TA) and tetracycline (TC) to enhance antibacterial and antibiofilm efficacy and to explore its potential involvement in efflux pump - related mechanisms. MATERIALS AND METHODS: MSNs were synthesized and loaded with TA and TC individually (MSN@TA, MSN@TC) and in combination (MSN@TA/TC). Physicochemical properties, including morphology, size, surface charge, and drug loading, were characterized. Antibacterial activity was assessed using MIC and MBC assays. Biofilm inhibition was evaluated by crystal violet staining, and NorA gene expression was measured by qPCR. RESULTS: MSNs were spherical with a size of 100-150 nm and a zeta potential of -45.8 mV. The co-loaded MSN@TA/TC showed superior antibacterial activity (MIC: 31.25 µg/mL; MBC: 62.5 µg/mL) compared to single-drug systems. Biofilm formation was reduced by 35-95% in a dose-dependent manner, with the highest inhibition observed for MSN@TA/TC. Moreover, NorA expression was downregulated by 4.5-fold following treatment. CONCLUSIONS: Co-encapsulation of TA and TC in MSNs significantly enhanced antibacterial and antibiofilm effects against S. aureus, likely through modulation of efflux pump-associated resistance. This nanocarrier system shows promise for improving antibiotic efficacy in biofilm-associated infections.