Aerosol Delivery to the Respiratory tract in Experimental Animals

The inhaled route is a convenient way to deliver drugs to the lung. Inhaled pharmaceutical drugs can either act locally in the lung or get absorbed into the systemic circulation to exert their effect. Since the lung functions as a filter it is important to know the optimal particle size distribution to get an optimal deposition in the lung for the species to be studied. In the search for better drugs for local treatment of inflammatory diseases in the respiratory tract it is important that new candidate drugs are evaluated in inhalation delivery systems that are well characterised. Aerosols can be delivered either nose-only or by intubating rats or dogs. An aerosol generator can be fitted to the inhalation chamber or to the nose mask which allows for the aerosol to be inhaled. Selective aerosol deposition in the lung can be achieved by use of the endotracheal tube. In both the above cases, the inhaled dose can be calculated from a filter sample drawn in the breathing zone of the animal during exposure. Simultaneously the aerosol can be monitored in real-time to measure changes in the particle concentration. This is an advantage as the aerosol concentration can be adjusted during delivery to give a more accurate dose to the animal. In our exposure systems, a tracer aerosol with Evans blue, is used to verify the estimated lung burden with the actual deposition patterns found in these animals. Finally we will also give an example of how the effect/side effects ratio can vary if a glucocorticosteroid (budesonide) is administered by different routes, and how the estimated inhaled dose correlates with the kinetic profile (area under the curve).