Influence of mesh nebulizer characteristics on aerosol delivery in non-human primates

Non-Human Primates (NHPs) are particularly relevant for preclinical studies during the development of inhaled biologics. However, aerosol inhalation in NHPs is difficult to evaluate due to a low lung deposition fraction and high variability. The objective of this study was to evaluate the influence of mesh nebulizer parameters to improve lung deposition in macaques. We developed a humidified heated and ventilated anatomical 3D printed macaque model of the upper respiratory tract to reduce experiments with animals. The model was compared to in vivo deposition using 2D planar scintigraphy imaging in NHPs and demonstrated good predictivity. Next, the anatomical model was used to evaluate the position of the nebulizer on the mask, the aerosol particle size and the aerosol flow rate on the lung deposition. We showed that placing the mesh-nebulizer in the upper part of the mask and in proximal position to the NHP improved lung delivery prediction. The lower the aerosol size and the lower the aerosol flow rate, the better the predicted aerosol deposition. In particular, for 4.3 +/- 0.1 mu m in terms of volume mean diameter, we obtained 5.6 % +/- 0.2 % % vs 19.2 % +/- 2.5 % deposition in the lung model for an aerosol flow rate of 0.4 mL/min vs 0.03 mL/min and achieved 16 % of the nebulizer charge deposited in the lungs of macaques. Despite the improvement of lung deposition efficiency in macaques, its variability remained high (6-21 %).