Efficient drug delivery to lung epithelial lining fluid by aerosolization of ciprofloxacin incorporated into PEGylated liposomes for treatment of respiratory infections.
OBJECTIVE
The efficacy of aerosolization of ciprofloxacin (CPFX) incorporated into PEGylated liposomes (PEGylated CPFX-liposomes) for the treatment of respiratory infections was evaluated.


METHODS
PEGylated CPFX-liposomes with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] (particle size: 100 nm) were prepared, and the drug distribution characteristics in lung epithelial lining fluid (ELF) following aerosolization of PEGylated CPFX-liposomes were examined in rats. Furthermore, the antibacterial effects of PEGylated CPFX-liposomes in ELF were evaluated by pharmacokinetic/pharmacodynamic analysis.


RESULTS
The elimination rate of CPFX from ELF following aerosolization of PEGylated CPFX-liposomes was significantly slower than that of CPFX incorporated into unmodified liposomes (unmodified CPFX-liposomes; particle size: 100 nm). According to pharmacokinetic/pharmacodynamic analysis, the PEGylated CPFX-liposomes exhibited potent antibacterial effects against pathogenic microorganisms in ELF.


CONCLUSIONS
This study shows that PEGylated CPFX-liposomes are a useful aerosol-based pulmonary drug delivery system for the treatment of respiratory infections.
Chono
Sumio
S
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, 7-1 Katsuraoka-cho, Otaru, Japan. s-chono@hokuyakudai.ac.jp
Suzuki
Hirokazu
H
Togami
Kohei
K
Morimoto
Kazuhiro
K
D000336:Aerosols / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004848:Epithelium / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008081:Liposomes / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy*
D000336:Aerosols; D000890:Anti-Infective Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D002939:Ciprofloxacin; D007770:L-Lactate Dehydrogenase