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

Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-beta-cyclodextrin (HP beta CD) 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/HP beta CD 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 H-1 NMR spectroscopy, confirming the successful HP beta CD inclusion of levofloxacin. The in vitro antibacterial effects of HP beta CD, levofloxacin, and the levofloxacin/HP beta CD inclusion complex against four different bacterial strains in liquid media and on agar plates were determined/compared (an MIC90 of 0.5-1.0 mu g/mL for the inclusion complex compared with that of 1.0-2.0 mu g/mL for free levofloxacin in liquid). Moreover, the in vivo antibacterial effects of levofloxacin and levofloxacin/HP beta CD 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/HP beta CD inclusion complex had an enhanced antibacterial activity compared with free levofloxacin. It implies that cyclodextrins (e.g. HP beta CD) may have a beneficial role when using as a chiral selector or as a drug nanocarrier for levofloxacin and that the levofloxacin/HP beta CD inclusion complex has the potential of being developed into a pharmaceutical for antibacterial therapies.