A Novel Aerosolization and Inhalation Platform for the Pulmonary Delivery of Anti-inflammatory Agents to Distal Airways for the Enhanced Pain Management in Chronic Obstructive Pulmonary Disease (COPD)

Project Summary Treating inflammation in deep lung would help manage pain in chronic obstructive pulmonary disease (COPD), as the pain is often associated with the prolonged induction of painful stimuli from hard-to-reach inflammations in distal airways. Current guidelines recommend pulmonary delivery of anti-inflammatory agents to treat COPD inflammations, however, existing technologies are limited by low deep lung deposition efficiencies, inadequate inspirations, poor medication adherence, and absence of point-of-care monitoring and dose control systems. Here, we propose a novel inhalation device equipped with a first-in-class atomizer for the pulmonary delivery of FDA-approved anti-inflammatory agents to the deep lung. Our prototype enables (1) verified ultrafine aerosol particle generation for superior deep lung deposition, outperforming nebulizers, (2) improved user interface requiring no hand-breath coordination unlike MDIs, and easy-to-use inspiratory flow (<2LPM, tidal-breath) unlike DPIs (>60LPM, strong inhalation), (3) a patented dose algorithm with SMART monitoring for individualized treatment. Our bottom-up atomization inhaler is distinct from vaping devices due to its: (1) Chemical Inertness, preventing side reactions, (2) Temperature Control and Dry Burn Protection, avoiding aerosol decomposition, and (3) Identity Verification, Remote Lock, and Touch ID, making it unattractive to vulnerable groups. Preliminary results have shown that NSIADs and other drug molecules can be pristinely aerosolized with appropriate aerodynamic sizes and no decomposition impurities, yielding a significant anti-inflammatory efficacy in vitro. In Aim 1, we plan to investigate the feasibility of aerosolizing and delivering two categories of anti-inflammatory agents, corticosteroids and NSAIDs, to distal airways via our novel device prototype. The investigation starts by developing formulations compatible with the atomizer and conducting rigorous aerosol analyses to quantify particle size, dosage, and chemical/thermal stability analysis. Then, we will employ established dosimetry models (MPPD and CFD) to estimate pulmonary deposition in simulated human respiratory tracts, providing quantitative insights into the therapeutic potential of our proposed inhalation prototype. In Aim 2, we plan to leverage an inflamed multicellular model (EpiAlveolar co-cultured with MDMs and CD8+ T cells, inflammation induced by LPS) to characterize the anti-inflammatory efficacies. The Apical Concentration (CA) will be measured from liquid (basal surface) and aerosol (apical surface), evaluating the quantitative dosage for the pulmonary delivery of repurposed anti-inflammatory agents. Other specific endpoints include cellular phenotype such as pro/anti-inflammatory reactions (i.e., cytokine expression), barrier integrity, cell viability, and gene expression of type I/II pneumocytes to determine efficacy and safety profiles of the aerosolized molecules. In future SBIR phase II, we target to validate the efficacy and safety in mice models with relative analgesic index (RAI) and anti-inflammation efficacy characterized towards the development of a commercially viable product.