AAAR 33rd Annual Conference
October 20 - October 24, 2014
Rosen Shingle Creek
Orlando, Florida, USA
Abstract View
In Vitro Aerosolized Antigen Dosimetry Lung Models
AYESHA MAHMOOD, John Dye, US Army Medical Research Institute for Infectious Disease
Abstract Number: 453 Working Group: Bioaerosols
Abstract The dynamics of aerosol deposition in the human airway is associated with the localized and systemic physiological responses. The quantitative measurement of droplet deposition for in vitro modeling of aerosol exposure is important to our understanding of human exposure to chemical and biological agents. Inhaled aerosols are of particular interest for the pharmaceutical evaluation and for better understanding of disease pathogenesis, with and without environmental irritant exposure. The overall objective of this work is to define simplified methods to quantify antigen weight and droplet size, to design biomimetic tissue models. To this end, the Lung Mucosal Tissue Equivalent module (MTE) was cultured with either upper (nasal) or lower (alveolar) respiratory track epithelial cells, to mimic the local respiratory environment. These tissue models exhibit distinctive transepithelial electrical resistance and permeability to inert FITC-dextran molecules. This work builds on the barrier function understanding of our lung MTE tissue models and utilizes the VitroCell system for controlled aerosol generation in vitro. The real-time quantitative measure of aerosol droplet deposition dynamics show that the aerosolized delivery can be controlled with droplet size range of 2.5-6um. Larger droplets of 4.5-6um were applied to the nasal MTE. Relatively smaller, 2.5-4um, droplets were applied to the alveolar MTE. The weight and size of the droplet deposition on the MTE was quantified with known concentrations of FITC-Dextran. The results demonstrate distinct differences between the size and weight of the droplets designed to mimic the upper and lower airway physiology. There was a range of cloud deposition profiles with each molecular weight of antigen. This variation is dependent on cloud settling profiles and somewhat anticipated in a dynamic delivery system. Compared to the nasal model, there was a higher degree of variance with the alveolar airway droplet deposition. The results confirm biomimetic inefficiency of aerosolized mode of delivery and define controllable parameters for future studies.