Enhanced Antibacterial\nActivity of Levofloxacin with\nCucurbit[7]uril-Functionalized Gold Nanoparticles

Bacterial infection is one of the major concerns of the\ngrowing\nsociety, and over the years, different permutations and combinations\nof various drugs and adjuvants have been attempted, which led to considerable\nimprovements in the efficacy of the antibacterial drugs. In this regard,\nmacrocyclic receptors such as cyclodextrin, cucurbiturils, calixarene,\netc., have played a major role by modulating the drug properties that\nsupplement the antibacterial efficacy. In this study, we have developed\ncucurbit[7]uril (CB7)-functionalized Au nanoparticles (CB7AuNPs) to\nmodulate the activity of an antibiotic, levofloxacin (LOFL). From\nthe spectroscopic and thermodynamic changes in the LOFL, it has been\nestablished that two of the prototropic forms, LOFLH and LOFLH<sub>2</sub><sup>+</sup>, form strong 1:1 host/guest complexes with CB7/CB7AuNP.\nBoth these interactions led to significant upward shifts in the p<i>K</i><sub>a</sub> values as well as photostability of LOFL,\nthereby enhancing the availability of the active form for the antibacterial\nactivity, at the physiological pH. Further, the LOFL uptake has also\nbeen established on CB7AuNP, which retained the CB7-LOFL activity\nat very low concentration of the CB7 host, functionalized on AuNP.\nDetailed antibacterial studies of LOFL, both as complexed with CB7\nand CB7AuNP, were carried out using four food-borne pathogens (Escherichia coli, S. Typhimurium, Bacillus cereus, and Staphylococcus aureus), which revealed a creditable\nenhancement in the antibacterial property, irrespective of the bacterium\nstrain. These results are quite promising at this stage for the development\nof drugs customized for multidrug-resistant bacteria.