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

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, Pre-ciseInhale, 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 flowrate 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 lL/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 lm, compared to the 4-5 lm droplets emitted by the nebulizer. Controlling the Aerogen nebulizer under a reduced output scheme within the Pre-ciseInhale 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.

Aerosolized delivery of ESKAPE pathogens for murine pneumonia models

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An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants

“…Seeking to maximize the exposure of HH-120 to SARS-CoV-2 viruses to improve its bioavailability, we evaluated whether HH-120 could be administrated via inhalation, which should support direct delivery of HH-120 (with a MW of ~1000 KDa) to the entire respiratory tract from the nose to lung, thus efficiently targeting the SARS-CoV-2 virus locally at the main infection sites. We choose a mesh vibrating nebulizer instrument (Aerogen Solo) that employs a mini pump to produce fine particles with geometric diameter range between 1–5 μm 42 (i.e., ideally sized particles for deep lung deposition 43 ). To evaluate the influence of nebulization on the physicochemical properties and neutralization activity of HH-120, HH-120 aerosols produced by the Aerogen Solo instrument were collected and analyzed: HH-120 exhibited the same SEC-HPLC peak profiles before and after nebulization, without notable aggregation or degradation, and the HH-120 main peak maintained at a high percentage level after nebulization (98.78%) as compared to that before nebulization (99.13%) (Supplementary Fig.…”

An IgM-like Inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2

“…Seeking to maximize the exposure of HH-120 to SARS-CoV-2 viruses to improve its bioavailability, we evaluated whether HH-120 could be administrated via inhalation, which should support direct delivery of HH-120 (with a MW of ~ 1000KDa) to the entire respiratory tract from the nose to lung, thus e ciently targeting the SARS-CoV-2 virus locally at the main infection sites. We choose a mesh vibrating nebulizer instrument (Aerogen Solo) that employs a mini pump to produce ne particles with geometric diameter range between 1-5 µm 39 (i.e., ideally sized particles for deep lung deposition 40 ). To evaluate the in uence of nebulization on the physicochemical properties and neutralization activity of HH-120, HH-120 aerosols produced by the Aerogen Solo instrument were collected and analyzed: HH-120 exhibited the same SEC-HPLC peak pro les before and after nebulization, without notable aggregation or degradation.…”