Aerosolized Liposomal Formulation Prevents Enhanced Drug Transfer from Fibrotic Lungs to the Systemic Circulation

(E-pub Ahead of Print)

Author(s): Kohei Togami*, Kaede Kurasho, Yukimune Kanehira, Hitoshi Tada, Sumio Chono

Journal Name: Current Drug Delivery

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Abstract:

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.

Keywords: Polyethylene glycolylated liposomes, bleomycin-induced pulmonary fibrosis, idiopathic pulmonary fibrosis, pulmonary drug delivery system, alveolar epithelial cells, NCI-H441, in vivo imaging

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1567201818666201229154143
Price: $95

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