Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. 1998

B K Leong, and J K Coombs, and C P Sabaitis, and D A Rop, and C S Aaron
Investigative Toxicology, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan, USA.

The effectiveness of three techniques to deliver a diazo dye suspension into the lungs of rats was compared. The intratracheal nebulization (ITN) technique delivered 10 microl of the suspension per 5-ml puff of air in 10 puffs as an aerosol. The intratracheal fast instillation (ITFI) technique delivered 100 microl of the suspension in a single 2-ml puff of air as droplets. The nose-only inhalation (NI) technique aerosolized the suspension at an analytical concentration that provided a calculated dose equivalent to 100 microl of the suspension in a 2-h inhalation period. Immediately after dosing, all the rats were killed by exsanguination. The trachea was tied and the lung was inflated in situ with air. After fixation, 5-microm thick slices were prepared from each lobe of the lung at a plane perpendicular to the axis of the lobar bronchus at levels proximal, medial and distal to the hilus. The numbers of bronchi, bronchioli and alveolar ducts within four ranges of diameters and the proportion of each selected area of lung tissue with and without dye particles were quantified using electronic imaging analyzers. The results indicated that ITN and ITFI dispersed the particles evenly throughout most of the airways and in patches in the alveoli. The NI technique dispersed the particles homogeneously throughout the airways and the alveoli in the lungs. The mean number-percentage and the mean area-percentage data revealed that the doses delivered by ITN and NI were approximately 60% and 10%, respectively, of the ITFI dose. Thus, the ITFI technique appeared to be most suitable for pulmonary absorption and disposition studies where dosage precision is of primary concern. The ITN technique would need further improvement to meet the requirements for dose precision and particle distribution. For both ITFI and ITN, particle size was apparently not a critical determinant for deposition. The NI technique is suitable for inhalation toxicity studies where the pattern and uniformity of particle deposition is the primary concern.

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
D009330 Nebulizers and Vaporizers Devices that cause a liquid or solid to be converted into an aerosol (spray) or a vapor. It is used in drug administration by inhalation, humidification of ambient air, and in certain analytical instruments. Atomizers,Inhalation Devices,Inhalators,Inhalers,Vaporizers,Nebulizers,Vaporizers and Nebulizers,Atomizer,Device, Inhalation,Devices, Inhalation,Inhalation Device,Inhalator,Inhaler,Nebulizer,Vaporizer
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D003979 Diazonium Compounds Azo compounds consisting of an aryl or alkyl group that is joined through two nitrogen atoms to an anion (R-N2+X-). Compounds, Diazonium
D004396 Coloring Agents Chemicals and substances that impart color including soluble dyes and insoluble pigments. They are used in INKS; PAINTS; and as INDICATORS AND REAGENTS. Coloring Agent,Dye,Dyes,Organic Pigment,Stain,Stains,Tissue Stain,Tissue Stains,Organic Pigments,Pigments, Inorganic,Agent, Coloring,Inorganic Pigments,Pigment, Organic,Pigments, Organic,Stain, Tissue,Stains, Tissue
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000281 Administration, Intranasal Delivery of medications through the nasal mucosa. Drug Administration, Intranasal,Administration, Intranasal Drug,Administration, Nasal,Intranasal Administration,Intranasal Drug Administration,Administrations, Intranasal,Administrations, Intranasal Drug,Administrations, Nasal,Drug Administrations, Intranasal,Intranasal Administrations,Intranasal Drug Administrations,Nasal Administration,Nasal Administrations
D000336 Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. 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

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