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  3. Visualizing the spatial localization of ciclesonide and its metabolites in rat lungs after inhalation of 1-μm aerosol of ciclesonide by desorption electrospray ionization-time of flight mass spectrometry imaging

Visualizing the spatial localization of ciclesonide and its metabolites in rat lungs after inhalation of 1-μm aerosol of ciclesonide by desorption electrospray ionization-time of flight mass spectrometry imaging

  • Int J Pharm. 2021 Feb 15;595:120241. doi: 10.1016/j.ijpharm.2021.120241.
Eiichi Yamamoto 1,  Yuhji Taquahashi 2,  Makiko Kuwagata 2,  Hirokatsu Saito 2,  Kohei Matsushita 3,  Takeshi Toyoda 3,  Futoshi Sato 4,  Satoshi Kitajima 2,  Kumiko Ogawa 3,  Ken-Ichi Izutsu 5,  Yoshiro Saito 6,  Yoko Hirabayashi 7,  Yasuo Iimura 8,  Masamitsu Honma 8,  Haruhiro Okuda 8,  Yukihiro Goda 8
Affiliations

Affiliations

  • 1 Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan. Electronic address: eyamamoto@nihs.go.jp.
  • 2 Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institutes of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
  • 3 Division of Pathology, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
  • 4 APS and Technology Center, Nihon Waters K.K., 1-3-12 Kitashinagawa, Shinagaw-ku, Tokyo 140-0001, Japan.
  • 5 Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
  • 6 Division of Medicinal Safety Science, National Institutes of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
  • 7 Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
  • 8 National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
PMID: 33484917 DOI: 10.1016/j.ijpharm.2021.120241
Abstract

Inhaled ciclesonide (CIC), a corticosteroid used to treat asthma that is also being investigated for the treatment of corona virus disease 2019, hydrolyzes to desisobutyryl-ciclesonide (des-CIC) followed by reversible esterification when exposed to fatty acids in lungs. While previous studies have described the distribution and metabolism of the compounds after inhalation, spatial localization in the lungs remains unclear. We visualized two-dimensional spatial localization of CIC and its metabolites in rat lungs after administration of a single dose of a CIC aerosol (with the mass median aerodynamic diameter of 0.918-1.168 μm) using desorption electrospray ionization-time of flight mass spectrometry imaging (DESI-MSI). In the analysis, CIC, des-CIC, and des-CIC-oleate were imaged in frozen lung sections at high spatial and mass resolutions in negative-ion mode. MSI revealed the coexistence of CIC, des-CIC, and des-CIC-oleate on the airway epithelium, and the distribution of des-CIC and des-CIC-oleate in peripheral lung regions. In addition, a part of CIC independently localized on the airway epithelium. These results suggest that distribution of CIC and its metabolites in lungs is related to both the intended delivery of aerosols to pulmonary alveoli and peripheral regions, and the potential deposition of CIC particles on the airway epithelium.

Keywords

Aerodynamic diameter; Inhalation; Lung deposition; Mass spectrometry imaging; Spatial localization.

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