Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections

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. (C) 2007 Elsevier B.V. All rights reserved.