title: Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections.
abstract: The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-liposomes) for the treatment of respiratory intracellular parasitic infections was evaluated. In brief, mannosylated CPFX-liposomes with 4-aminophenyl-a-d-mannopyranoside (particle size: 1000 nm) were prepared, and the drug targeting to alveolar macrophages (AMs) following pulmonary administration was examined in rats. Furthermore, the antibacterial and mutant prevention effects of mannosylated CPFX-liposomes in AMs were evaluated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The targeting efficiency of CPFX to rat AMs following pulmonary administration of mannosylated CPFX-liposomes was significantly greater than that of CPFX incorporated into unmodified liposomes (unmodified CPFX-liposomes; particle size: 1000 nm). According to PK/PD analysis, the mannosylated CPFX-liposomes exhibited potent antibacterial effects against many bacteria although unmodified CPFX-liposomes were ineffective against several types of bacteria, and the probability of microbial mutation by mannosylated CPFX-liposomes was extremely low. The present study indicates that mannosylated CPFX-liposomes as pulmonary administration system could be useful for the treatment of respiratory intracellular parasitic infections.
authors.affiliation: Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, 7-1 Katsuraoka-cho, Otaru-city 047-0264, Japan. s-chono@hokuyakudai.ac.jp
authors.forename: Sumio
authors.initials: S
authors.lastname: Chono
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Tanino
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008362:Mannosides / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D011014:Pneumonia; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology / Q000469:parasitology; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D008362:Mannosides; D002939:Ciprofloxacin