Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation

Particles can be delivered to the respiratory tract of animals using various techniques. Inhalation mimics environmental exposure but requires large amounts of aerosolized NPs over a prolonged dosing time, varies in deposited dose among individual animals, and results in nasopharyngeal and fur particle deposition. Although less physiological, intratracheal (IT) instillation allows quick and precise dosing. Insufflation delivers particles in their dry form as an aerosol. We compared the distribution of neutron-activated (CeO2)-Ce-141 nanoparticles (5mg/kg) in rats after (1) IT instillation, (2) left intrabronchial instillation, (3) microspraying of nanoceria suspension and (4) insufflation of nanoceria dry powder. Blood, tracheobronchial lymph nodes, liver, gastrointestinal tract, feces and urine were collected at 5min and 24h post-dosing. Excised lungs from each rat were dried at room temperature while inflated at a constant 30cm water pressure. Dried lungs were then sliced into 50 pieces. The radioactivity of each lung piece and other organs was measured. The evenness index (EI) of each lung piece was calculated [EI = (Ci/mg(piece))/(Ci/mg(lung))]. The degree of EI value departure from 1.0 is a measure of deposition heterogeneity. We showed that the pulmonary distribution of nanoceria differs among modes of administration. Dosing by IT or microspraying resulted in similar spatial distribution. Insufflation resulted in significant deposition in the trachea and in more heterogeneous lung distribution. Our left intrabronchial instillation technique yielded a concentrated deposition into the left lung. We conclude that animal dosing techniques and devices result in varying patterns of particle deposition that will impact biokinetic and toxicity studies.