Abstract
Background: Many substances used in inhalation research are water soluble and can be administered as nebulized solutions. Typical examples are therapeutic, small-molecular agents, or macromolecules. Another category is a number of water-soluble agents used for airway diagnostics or disease modeling. Mesh nebulizers have facilitated well-controlled liquid aerosol exposures. Meanwhile, a benchtop inhalation platform, PreciseInhale, was developed for providing small-scale, well-controlled aerosol exposures in preclinical configurations. The purpose of the current research was to adapt the Aerogen mesh nebulizer to work within the PreciseInhale system for both cell culture and rodent exposures.Methods: The wet aerosols produced with the Aerogen Pro nebulizer were dried out in an aerosol holding chamber by supplying dry carrier air, which was provided by passing the incoming ambient air through a column with silica gel. The nebulizer was installed in an aerosol holding chamber between an upstream flow-rate pneumotach and a downstream aerosol monitor. By pulsing, the nebulizer output was reduced to 1%–10% of continuous operation to better match the exposure ventilation requirements. Additional drying was obtained by mantling the holding chamber with dried paper.Results and Conclusions: The nebulizer output was reduced to 3–30 μL/min and dried out before reaching the in vitro or in vivo exposure modules. Using solute concentrations in the range of 0.5%–2% (w/w), dried aerosols were produced with a mass median aerodynamic diameter of 1.5–2.0 μm, compared to the 4–5 μm droplets emitted by the nebulizer. Controlling the Aerogen nebulizer under a reduced output scheme within the PreciseInhale platform gave two major advantages: (i) by reducing aerosol output to better match exposure flow rates of single rodents, increased airway deposition yields were obtained in a range of 1%–10% relative to the nebulized amount of test substance and (ii) shrinking aerosol particle sizes through drying improved the peripheral lung deposition of test aerosols.
Highlights
Many substances used in inhalation research are water soluble and can be administered as nebulized solutions
The aerosol particle size was reduced by supplying dry carrier air to the inlet pneumotach at a flow rate with a capacity to receive humidity in 10–20% excess of what was needed to completely evaporate the generated wet aerosol
The Aerogen Pro mesh nebulizer combined with the dynamic vacuum system for the liquid container was integrated into the PreciseInhale platform to allow a controlled generation and delivery of nebulized aerosols
Summary
Many substances used in inhalation research are water soluble and can be administered as nebulized solutions. If the test substance is water soluble enough to be delivered as true aqueous solutions, the convenience and ease of use of modern mesh nebulizers merits the option of being able to choose liquid aerosol exposures. Mesh nebulizers such as the Aerogen (Aerogen, Ltd., Galway, Ireland) have been in use for over a decade,(1) both in the clinic and in various preclinical exposure uses with larger animals,(2) smaller animals/rodents,(3,4) and cell culture models.[5] It has a high aerosol output in the upper respirable size range[6] that is suitable to expose single subjects with larger lungs or multiple rodents at a time.
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