Collections > Electronic Theses and Dissertations > Development and Characterization of PRINT® Particles as Drug Delivery Vehicles in the Lung
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The aim of this dissertation is to develop and investigate the utility of the Particle Replication in Non-wetting Templates (PRINT®) technology as a toolbox to generate precisely defined particles in shape, matrix, and surface functionality to further the understanding of particulate drug delivery to the lung. The pulmonary route of administration is of particular interest in analyzing the effects of particles due to the vast exposure of our lungs to a wide array of airborne particulates. From pollen to bacteria to diesel exhaust, the fate and physiological impacts of these particulates cause a multitude of disease states in the human body. Understanding, and even harnessing, the specific characteristics which make these airborne invaders so potent at evading or wreaking havoc on the body's defense systems will hopefully lead to the development of more safe and efficient drug delivery vehicles. Particles of varying geometries were fabricated and shape effects on macrophage internalization in vitro were investigated to explore physical particle characteristics that may impart the ability to tailor alveolar macrophage uptake for use in pulmonary therapeutics. PEG particles ranging from 80x320 nm to 6 µm in diameter were instilled into the lungs of mice and cellular uptake, residence time, and inflammatory responses in the lung were analyzed. Being able to precisely tune individual particle parameters allowed for the determination of specific characteristics that could target or de-target specific cell populations in the lung. These PRINT particles were also shown to reside in the lung out to twenty-eight days without inducing an inflammatory response which demonstrates the potential of these particles as immunologically inert drug carriers to the lung.