Antimicrobial and antibiofilm activity of prepared thymol@UIO-66 and thymol/ZnONPs@UIO-66 nanoparticles against Methicillin-resistant Staphylococcus aureus: A synergistic approach

Abstract

This study introduces a novel approach to enhance the antibacterial properties of UIO-66 by incorporating both Thymol and ZnO nanoparticles within its framework which represents a significant advancement like exhibiting a synergistic antibacterial effect, providing a prolonged and controlled release, and mitigating cytotoxicity associated with the release of free ZnO nanoparticles by combining these two antimicrobial agents within a single, well-defined metal-organic framework. UIO-66 frameworks are investigated as carriers for the natural antimicrobial agent, Thymol, and ZnONPs offering a novel drug delivery system for antibacterial applications. Results demonstrated 132, 90, 184, and 223 nm sizes for UIO-66, ZnONPs, UIO-66 encapsulated Thymol, and UIO-66 encapsulated both Thymol and ZnONPs, respectively. Successful encapsulation of the antibacterial drug with a high entrapment efficiency of 64 % for Thymol was approved, and 49 % in-vitro release of Thymol was achieved for 72 hours. In-vitro antibacterial assays revealed promising results, with the drug-loaded nanoparticles exhibiting significantly lower MIC values and enhanced bactericidal activity against S. Aureus bacterial strains compared to the free drug, as demonstrated by agar disk diffusion and time-kill assays. MIC values reduced from a range of 31.25-250 µg/ml for free Thymol and 12.5-100 µg/ml for free ZnONPs to 3.9-62.5 µg/ml for Thymol@UIO-66 and 1.95-15.63 µg/ml for Thymol/ZnONPs@UIO-66. According to the results, the mixture of both Thymol and ZnONPs had 41 % and 16 % more antibiofilm activities in comparison with free Thymol and free ZnONPs, respectively. Furthermore, Thymol@UIO-66 had 25 % higher antibiofilm activities relative to not-encapsulated Thymol and ZnONPs, and this improvement was even 46 % more in Thymol/ZnONPs@UIO-66 in comparison with Thymol@UIO-66. Overall, this study demonstrates the potential of Thymol/ZnONPs@UIO-66 frameworks as a promising drug delivery platform for effective antibacterial therapy. This approach to overcome antibiotic resistance and improve treatment efficacy potentially.

Keywords: Anti-biofilm activities; Antibacterial activity; Thymol; UIO-66 frameworks; Zinc oxide nanoparticles.