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

Abstract

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 ¹⁴¹CeO₂ nanoparticles (5 mg/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 5 min and 24 h post-dosing. Excised lungs from each rat were dried at room temperature while inflated at a constant 30 cm 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 = (μCi/mg_piece)/(μCi/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.

Keywords:

• Aerosol delivery
• biokinetics
• insufflation
• intratracheal instillation
• microspray instillation
• nanoparticles
• pulmonary particle
• retention

Acknowledgements

The authors thank Drs. Phil Demokritou and Jiayuan Zhao for technical help and Melissa Curran for editorial assistance.

Declaration of interest

The authors declare no conflicts of interest in this paper.

This study was supported by the National Institutes of Health grant ES000002, The Hoffman Program in Health and Chemicals and MannKind Corporation. H.H. received support from the Science without Borders Program of Brazil administered by CAPES, the Brazilian Coordinating Office for the Advancement of Higher Education.