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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.  81m Kr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with  99m Tc-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.  81m Kr gas-ventilation and  99m Tc-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.

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