10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Intranasal and Tracheal Deposition of Dry Particles in 3D Physical Models of Rhesus Macaques
JANA KESAVAN, Valerie J. Alstadt, Jerold Bottiger, Beth Laube, US ARMY ECBC
Abstract Number: 1354 Working Group: Aerosols in Medicine
Abstract Background: Quantification of particle deposition in the respiratory system of animals is used to assess environmental exposures and the effectiveness of drug delivery. In particular, assessments of toxicological agents and vaccine delivery are often conducted in rhesus macaques and the results are extrapolated to humans. Since rhesus macaques are obligate nose-breathers, it is important to know the percentage of inhaled particles that is lost to deposition in the intranasal airways and trachea and the percentage that is available for delivery to the lungs to make accurate exposure assessments. However, little is known of intranasal and tracheal deposition in rhesus macaques and less is known about dry power deposition in these animals, since most studies are conducted with liquid particles and do not quantify intranasal and tracheal deposition. Because the approval process is long and testing is expensive in live animals, we chose to address this information gap using 3D-printed, anatomically-correct models of rhesus macaques. Methods: Five models were generated from the CT scans of the head and trachea of four female macaques and one male macaque, using 3D-printing technology. The monkeys ranged in age from 3-9 years of age. The models contained the intranasal region (i.e. nasal passage, pharynx, larynx) and the trachea. Deposition fraction was determined using solid polydispersed Arizona Test Dust (ATD) aerosols that contained dry particles ranging in size between 0.5 to 10 microns. Models were individually placed in a chamber and were connected to a vacuum pump that pulled a constant airflow at 2, 4 or 6 L/min through the model. An Aerodynamic Particle Sizer (APS) was used to measure the particle size and the concentration of the test aerosol that entered the nose (upstream aerosol concentration) and exited the trachea (downstream concentration). Approximately 0.06 g of ATD was aerosolized into the chamber and the air was mixed for 45 seconds to obtain uniform aerosol concentration in the chamber. The APS sampled the upstream and downstream aerosol concentrations for 20 seconds. Deposition fraction was calculated for each run by dividing the downstream measurement by the average of the preceding and following upstream measurements. Deposition fraction was expressed as a combination of deposition in the intranasal and tracheal regions. Deposition fraction was plotted as a function of particle size and impaction parameter (diameter squared multiplied by air flow rate). Results: Deposition fraction in the intranasal and tracheal regions combined increased as particle size and/or air flow rate increased and as the impaction parameter increased. Three of the models had similar deposition curves, whereas the other two models had higher deposition curves when the data were plotted as a function of impaction parameter. Deposition efficiency curves for three of the models indicated only 10% deposition for the impaction parameter of 1000 µm2 cm3 s-1. Deposition efficiency curves for the other two models showed approximately 50% and 65% deposition for the same impaction parameter. Conclusions: These findings indicate there was significant variability in the deposition of dry particles in the intranasal and tracheal regions of the 3D-printed models of these rhesus macaques. Such variability suggests there could be significant differences in dry particle deposition in the lungs of these animals as well, which differences could ultimately affect individual animal responses to toxic and therapeutic agents, thereby affecting interpretation of the data. Additional studies using this model approach could provide much needed information about deposition of dry particles in the intranasal and tracheal regions of rhesus macaques, which could lead to more accurate interpretations of toxic and therapeutic environmental exposures, without exposing the animal to the inhaled agents.