Researcher(s)
- Nicole Gill, Chemical Engineering, University of Delaware
Faculty Mentor(s)
- Catherine Fromen, Chemical Engineering, University of Delaware
Abstract
Approximately 544.9 million people globally are diagnosed with chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and tuberculosis; furthermore, this number has increased 39.8% since 1990. [1 ] Despite respiratory diseases mainly affecting the lungs, many of the current therapeutics to treat these diseases are systemic and do not directly target the lungs. Although less commonly used, pulmonary drug delivery can establish high concentrations of drug in the airways and targeted tissues, while lowering the absorption in other parts of the body, which avoids unfavorable side effects or the development of drug resistance. [2] In researching new possibilities for aerosolized drugs, it is important to understand their effects on the immune system. In this research we investigate how the phagocytosis of aerosol nanoparticle drug carriers affects the intracellular signaling of pulmonary immune cells. Previous research from the Fromen lab has found that bone marrow-derived macrophages (BMMs) have an increased survival, as well as secrete an unknown, pro-survival signal that increases the survival of otherwise untreated BMMs when dosed with inert polyethylene glycol (PEG) nanoparticles (NPs). In this research, cell survival studies with and without NPs were conducted using cell imaging to derive a relationship between NP uptake, cell secretion, and cell survival. Proteomics and mass spectroscopy were also performed on the supernatant of the cells secreting the pro-survival signal to obtain data to identify the unknown secreted signal. Additionally, a cellular analysis in the presence of NPs was carried out using both live cell imaging and staining of fixed cells to test how the NPs affect the structure of the macrophages. The imaging of both the live and stained cells was done using the Agilent Biotek Cytation 5 with 4X, 20X, and 80X magnification, and TexasRed, DAPI, and GFP channels. Finally, the physical effects of nanoparticle loading into nebulized aerosols was explored in order to create aerosols with tunable nanoparticle loadings and aerosol sizes. Formulations of different concentrations of nanoparticles were aerosolized with an Aeroneb vibrating mesh nebulizer, and the resulting aerosols were characterized by laser diffraction using an optical particle sizer (OPS). Overall, the results from this work could be used in vaccine development to control the quality and duration of immune response, as well as create aerosol formulations that can be tuned to reach specific lung deposition targets.
References:
(1) Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020, 8 (6), 585-596. DOI: 10.1016/s2213-2600(20)30105-3 From NLM.
(2) Restrepo, M. I.; Keyt, H.; Reyes, L. F. Aerosolized Antibiotics. Respiratory Care 2015, 60 (6), 762. DOI: 10.4187/respcare.04208.