Abstract
The efficacy of pulmonary administration of liposomal ciprofloxacin (CPFX) in pneumonia was evaluated. In brief, the pharmacokinetics following pulmonary administration of liposomal CPFX (particle size, 1,000 nm; dose, 200 μg/kg) were examined in rats with lipopolysaccharide-induced pneumonia as an experimental pneumonia model. Furthermore, the antibacterial effects of liposomal CPFX against the pneumonic causative organisms were estimated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The time-courses of the concentration of CPFX in alveolar macrophages (AMs) and lung epithelial lining fluid (ELF) following pulmonary administration of liposomal CPFX to rats with pneumonia were markedly higher than that following the administration of free CPFX (200 μg/kg). The time course of the concentrations of CPFX in plasma following pulmonary administration of liposomal CPFX was markedly lower than that in AMs and ELF. These results indicate that pulmonary administration of liposomal CPFX was more effective in delivering CPFX to AMs and ELF compared with free CPFX, and it avoids distribution of CPFX to the blood. According to PK/PD analysis, the liposomal CPFX exhibited potent antibacterial effects against the causative organisms of pneumonia. This study indicates that pulmonary administration of CPFX could be an effective technique for the treatment of pneumonia.
ACKNOWLEDGEMENTS
This work was supported in part by a grant-in-aid (16590117) for Scientific Research provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan and in part by a grant-in-aid (2005) provided by The AKIYAMA foundation (Sapporo, Japan). This work was also supported in part by the education and research fellowship (2005) provided by Hokkaido Pharmaceutical University. We thank Nikkiso Co., Ltd. (Tokyo, Japan) for help with the zeta potential analysis. We also thank Elizabeth Vasievich (School of Pharmacy, University of North Carolina at Chapel Hill) for her help in preparing the manuscript.