Pulmonary distribution of nanoceria: comparison of intratracheal, microspray instillation and dry powder insufflation. 2016

Ramon M Molina, and Nagarjun V Konduru, and Hugo Hirano, and Thomas C Donaghey, and Benoit Adamo, and Brendan Laurenzi, and Georgios Pyrgiotakis, and Joseph D Brain
a Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health , Boston , MA , USA and.

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/mgpiece)/(μCi/mglung)]. 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.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009502 Neutrons Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. Neutron
D011208 Powders Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed) Powder
D002563 Cerium An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications.
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014132 Trachea The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. Tracheas
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D053768 Metal Nanoparticles Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver. Metal Nanocrystals,Metallic Nanocrystals,Metallic Nanoparticles,Metal Nanocrystal,Metal Nanoparticle,Metallic Nanocrystal,Metallic Nanoparticle,Nanocrystal, Metal,Nanocrystal, Metallic,Nanocrystals, Metal,Nanocrystals, Metallic,Nanoparticle, Metal,Nanoparticle, Metallic,Nanoparticles, Metal,Nanoparticles, Metallic

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