Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model

The knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles. An ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 μm-0.5 μm], [0.25 μm-1 μm] and [1 μm-9 μm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract. Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing. Planar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub-micron to micron The deposited fractions obtained, for thoracic vs. extra-thoracic regions respectively, were 89 ± 4 % vs. 11 ± 4 % for [0.15 μm-0.5 μm], 78 ± 5 % vs. 22 ± 5 % for [0.25 μm-1 μm] and 35 ± 11 % vs.65 ± 11 % for [1 μm-9 μm]. Results obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans.