A novel method for studying airway hyperresponsiveness in allergic guinea pigs in vivo using the PreciseInhale system for delivery of dry powder aerosols

Abstract

Inhaled adenosine receptor agonists induce bronchoconstriction and inflammation in asthma and are used as bronchial challenge agents for the diagnosis of asthma and in respiratory drug development. Recently developed dry powder aerosols of adenosine have several advantages over nebulised adenosine 5′-monophosphate (AMP) as bronchial challenge agents. However, reverse translation of this bronchial challenge technique to pre-clinical drug development is limited by the difficulty of administering powder aerosols to animals. The aim of the current study was to develop methods for delivering powder aerosols of adenosine receptor agonists to sensitised guinea pigs (as a model of allergic asthma) and evaluate their effect as challenge agents for the measurement of airway responsiveness. The PreciseInhale system delivered micronised AMP and adenosine powders, with mass median aerodynamic diameters of 1.81 and 3.21 μm and deposition fractions of 31 and 48% in the lungs, respectively. Bronchoconstrictor responses in passively sensitised, anaesthetised, spontaneously breathing guinea pigs were compared to responses to nebulised and intravenously administered AMP and adenosine. AMP- and adenosine-induced bronchoconstriction following all routes of administration with the magnitude of response ranking intravenous > dry powder > nebulisation, probably reflecting differences in exposure to the adenosine agonists delivered by the different routes. In conclusion, the PreciseInhale system delivered AMP and adenosine dry powder aerosols accurately into the lungs, suggesting this method can be used to investigate drug effects on airway responsiveness.

Pulmonary immunization: deposition site is of minor relevance for influenza vaccination but deep lung deposition is crucial for hepatitis B vaccination

“…However, one of the major limitations associated with this device is the use of high-pressure pulse for the dispersion of dry powders. In a study of Lexmond et al 18 ,. this resulted in the crystallization of amorphous spray-dried products thereby forming large agglomerates.…”

The Generation of a Comprehensive Spectral Library for the Analysis of the Guinea Pig Proteome by SWATH‐MS

“…The guinea pig is an excellent experimental model for many aspects of human physiology and pathophysiology—including maternal and fetal adaptations to pregnancy cardiac excitation‐contraction coupling, asthma and airway drug responsiveness, auditory somatosensory processes, type 2 diabetes, and vitamin C deficiency—yet there is limited experimental information regarding the proteome available for this species. In an effort to overcome this obstacle, we therefore sought to generate a detailed spectral library of the guinea pig proteome.…”

Adapting the Aerogen Mesh Nebulizer for Dried Aerosol Exposures Using the PreciseInhale Platform

“…(27) Another large group of substances where in-line drying of nebulizer aerosols can be useful is the variety of reasonably water-soluble compounds that are used to induce and titrate airway hyperresposiveness in preclinical rodent models, such as lipopolysaccarides, (28) house dust mite extracts, adenosine, (29) ovalbumine, and the methacholine, tested here. (30)(31)(32) Another pretreatment procedure where inhalation of highly respirable aerosols may improve outcome accuracy is with rodent fibrotic models using bleomycin. (33,34) Providing these substances to the lungs as respirable aerosols with higher precision, instead of being instilled as liquids or insufflated as powders to the test subject lungs, may improve the statistical resolution of subsequent experiments.…”