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 minutes and 24 hours 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 (El) 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.

Niclosamide Inhalation Powder Made by Thin-Film Freezing: Pharmacokinetic and Toxicology Studies in Rats and Hamsters

“…Moreover, they detected higher amounts of their formulation in the gastrointestinal tract, suggesting mucociliary clearance from the upper respiratory tract. They speculated that the deposition in the trachea was related to issues in the synchronization between the insufflation and the inhalation cycle of the animals and not due to properties of the drug [42]. The work of Duret et al (2012) confirms that the DP-4M® insufflator (used in this study) is reliable for delivering different drug doses of the same powder in mice, but unfortunately, in their work, the animals were immediately sacrificed to measure drug deposition [43].…”

“…We hypothesize that the administration of a higher dose of powder caused a change in aerosolization properties from the dry powder insufflator used to administer the dose of powder to the hamsters. Molina et al (2016) compared different methods of pulmonary administration of nanoparticles, and they found that with dry powder insufflation, the nanoparticles were cleared faster because the powder was deposited in the larger airways and trachea with higher variability among the animals (i.e., 188%). Moreover, they detected higher amounts of their formulation in the gastrointestinal tract, suggesting mucociliary clearance from the upper respiratory tract.…”

Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice

“…Compared with aerosol inhalation, intratracheal administration can decrease dose loss and better represent the relationship between dosage and pathological changes 33 . However, one of limitations in the use of intratracheal instillation in animal models is that particulates may be unevenly distributed and accumulate in some sections of the lungs after PM 2.5 instillation 34 , 35 . Another limitation is that intractracheally instilled PM 2.5 may not reproduce the pathological reactions induced by inhaled PM 2.5 .…”

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

“…PennCentury produced a hand-operated dry powder insufflator TM to aerosolize dry powders and deliver fine particles for small rodent applications (Codrons, Vanderbist, Ucakar, Préat, & Vanbever, 2004). Molina et al (Molina et al, 2016) compared CeO2 (cerium oxide) nanoparticles distribution from intratracheal instillation and powder insufflation using Penn-Century device. It is found that inhalation insufflation caused a more significant deposition in the trachea and a more uniform particle distribution within lungs than instillation.…”