Jiangxi Key Laboratory for Microscale interdisciplinary Study, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330031, PR China.
Jiangxi Key Laboratory for Microscale interdisciplinary Study, Institute for Advanced Study, Nanchang University, Nanchang, Jiangxi 330031, PR China.
Colloids Surf B Biointerfaces. 2022 Jul;215:112514. doi: 10.1016/j.colsurfb.2022.112514. Epub 2022 Apr 27.
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 H 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 MIC 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.
左氧氟沙星是氧氟沙星（一种氟喹诺酮类抗菌药物）的左旋对映异构体。环糊精（CDs），包括羟丙基-β-环糊精（HPβCD），通常被用作一些药物（包括左氧氟沙星）的对映体拆分的手性选择剂，或作为许多药物的药物/食品纳米载体以提高疗效。我们假设环糊精包合有可能进一步提高左氧氟沙星的抗菌活性。为了验证这一假设，通过冷冻干燥法制备了左氧氟沙星/HPβCD 包合物，并通过相溶解度图、差示扫描量热法（DSC）、X 射线衍射（XRD）、紫外可见分光光度计和 H NMR 光谱进行了表征，证实了 HPβCD 成功包合了左氧氟沙星。在液体介质中和琼脂平板上，测定/比较了 HPβCD、左氧氟沙星和左氧氟沙星/HPβCD 包合物对四种不同细菌株的体外抗菌作用（包合物的 MIC 为 0.5-1.0μg/mL，而游离左氧氟沙星的 MIC 为 1.0-2.0μg/mL）。此外，通过金黄色葡萄球菌感染小鼠的皮肤烫伤模型，测试了左氧氟沙星和左氧氟沙星/HPβCD 包合物的体内抗菌作用，发现包合物处理后烫伤皮肤中的细菌和白细胞数量减少。数据显示，与游离左氧氟沙星相比，左氧氟沙星/HPβCD 包合物具有增强的抗菌活性。这意味着环糊精（如 HPβCD）在用作手性选择剂或作为左氧氟沙星的药物纳米载体时可能具有有益作用，并且左氧氟沙星/HPβCD 包合物有可能被开发成一种用于抗菌治疗的药物。
