Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory disease characterized
by the destruction of the alveolar structure. In pulmonary fibrosis, aerosolized drugs are easily transferred to the systemic
circulation via leakage through the injured alveolar epithelium. Therefore, pulmonary drug delivery systems for sustained
distribution in fibrotic lungs are needed.
Objective: We evaluated the intrapulmonary pharmacokinetics of aerosolized liposomes as pulmonary drug delivery
systems in mice with bleomycin-induced pulmonary fibrosis.
Methods: The aerosolized liposomal formulations and solutions of model compounds, including indocyanine green and 6-
carboxyfluorescein (6-CF), were intrapulmonarily administered to mice with bleomycin-induced pulmonary fibrosis. In vivo
imaging for indocyanine green and 6-CF measurements in lung tissues and plasma were performed. Additionally, in vitro
permeation experiments using NCI-H441 cell monolayers as a model of alveolar epithelial cells were performed.
Results: The fluorescence signals of indocyanine green following the administration of liposomal formulations were
observed longer in the lungs than those in solution-treated mice. Compared with the solution, the 6-CF concentrations in
lung tissues after the administration of liposomal formulations were determined higher, whereas those in the plasma were
lower. 6-CF permeability was significantly increased by transforming growth factor-β1 in NCI-H441 cell monolayers treated
with the solution but unchanged in the presence of the liposomal formulation.
Conclusion: The aerosolized liposomal formulation can prevent enhanced drug transfer from fibrotic lungs into the
systemic circulation via the injured alveolar epithelium. This system may be useful for the sustained distribution of antifibrotic agents in fibrotic lungs and the optimization of IPF therapy.