2023 AIChE Annual Meeting
Designing Nanoparticle-Loaded Aerosols for Controlled Interactions with Pulmonary Immune Cells for Treatment of Respiratory Diseases
Approximately 544.9 million people globally are diagnosed with chronic respiratory diseases, which has increased 39.8% since 1990 (Lancet Respiratory Medicine, 2020). Aerosolized drugs that can yield controlled effects on the pulmonary immune system may afford new opportunities to treat such diseases. In this research, we investigate the role of nanoparticle (NP) formulations as respirable drug delivery carriers. We first investigate how the phagocytosis of NPs affects the intracellular signaling of pulmonary immune cells. Cell survival studies using bone marrow-derived macrophages (BMMs) dosed with inert polyethylene glycol (PEG) NPs were conducted to derive a relationship between NP uptake, cell secretion, and cell survival. We demonstrated that NP-dosed BMMs drive secretion of pro-survival signals that increases the lifespan of untreated BMMs. To deliver these PEG NPs to the lung, we next explored the physical effects of NP loading into nebulized aerosols to create respirable aerosols with tunable sizes. Formulations of different concentrations of NPs were aerosolized with an Aeroneb vibrating mesh nebulizer and characterized by laser diffraction. We find that at a critical NP concentration, the aerosol volumetric median diameter increased upwards of ~150%. On-going work includes combining these effects to study bio-active NPs for immune and gene delivery applications.