Enhanced antibacterial activity of levofloxacin/hydroxypropyl-β-cyclodextrin inclusion complex: In vitro and in vivo...

Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-β-cyclodextrin (HPβCD) are generally used as a chiral selector for the enantioseparation of some drugs including levofloxacin or as a drug/food nanocarrier for the efficacy improvement of many pharmaceuticals. We hypothesized that the cyclodextrin inclusion is potentially able to further improve the antibacterial activity of levofloxacin. To test this hypothesis, the levofloxacin/HPβCD inclusion complex was prepared by the freeze-drying method and characterized by phase solubility diagram, differential scanning calorimetry (DSC), X-ray diffractometry (XRD), UV-Vis spectrophotometer, and ¹H NMR spectroscopy, confirming the successful HPβCD inclusion of levofloxacin. The in vitro antibacterial effects of HPβCD, levofloxacin, and the levofloxacin/HPβCD inclusion complex against four different bacterial strains in liquid media and on agar plates were determined/compared (an MIC₉₀ of 0.5-1.0 μg/mL for the inclusion complex compared with that of 1.0-2.0 μg/mL for free levofloxacin in liquid). Moreover, the in vivo antibacterial effects of levofloxacin and levofloxacin/HPβCD inclusion complex were tested by using a skin scald model in mice infected with Staphylococcus aureus, and decreased amounts of both bacteria and leukocytes were detected in scalded skin after the inclusion complex treatment. The data revealed that the levofloxacin/HPβCD inclusion complex had an enhanced antibacterial activity compared with free levofloxacin. It implies that cyclodextrins (e.g. HPβCD) may have a beneficial role when using as a chiral selector or as a drug nanocarrier for levofloxacin and that the levofloxacin/HPβCD inclusion complex has the potential of being developed into a pharmaceutical for antibacterial therapies.