Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies

Sci Rep. 2019 Nov 29;9(1):17949. doi: 10.1038/s41598-019-54479-2.

Abstract

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols / administration & dosage*
  • Aerosols / pharmacokinetics
  • Animals
  • Biomechanical Phenomena
  • Disease Models, Animal
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / physiopathology*
  • Lung / drug effects
  • Lung / physiopathology*
  • Respiration / drug effects
  • Single Photon Emission Computed Tomography Computed Tomography
  • Swine
  • Technetium Tc 99m Pentetate / analysis

Substances

  • Aerosols
  • Technetium Tc 99m Pentetate