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Optimization and dose estimation of aerosol delivery to non-human primates

MacLoughlin, Ronan J.
; 
van Amerongen, Geert
; 
Fink, James B.
; 
Janssens, Hettie M.
; 
Duprex, W. Paul
; 
de Swart, Rik L.
Identifiers
http://hdl.handle.net/10379/12556
 https://doi.org/10.13025/28570
Publication Date
2016-06-01
Keywords
cynomolgus macaques, inhaled dose, non-human primates, tidal breathing, vibrating mesh nebulizer, pulmonary vaccine delivery, respiratory-function, young-children, deposition, challenges, facemasks, therapy, inhaler, infants, system
Type
Article
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Citation
MacLoughlin, Ronan J. van Amerongen, Geert; Fink, James B.; Janssens, Hettie M.; Duprex, W. Paul; de Swart, Rik L. (2016). Optimization and dose estimation of aerosol delivery to non-human primates. Journal of Aerosol Medicine and Pulmonary Drug Delivery 29 (3), 281-287
Abstract
Background: In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. Methods: Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5 kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. Albuterol was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. Results: Tidal volumes ranged from 24 to 46 mL, breathing frequencies from 19 to 31 breaths per minute and I: E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. Conclusions: Studies in non-human primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account.
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Publisher
Mary Ann Liebert Inc
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)