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Type of Resource (primo): dissertations
Name: Personal
Name: Personal
Name: Personal
Name: Personal
Name: Corporate
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Note: thesis: Thesis (Sc. M.)--Brown University, 2023
Genre (aat): theses
Abstract: The use of soft, cell-like microparticles as a carrier for drug nanocrystals holds great promise in the drug delivery field. Research shows that microparticles with similar elastic properties to mammalian cells allow them to bypass organs, leading to longer circulation times in-vivo. The goal of this study was to characterize and compare soft, 0.25 kPa hyper-compliant polyacrylamide microparticles to stiff, 10 kPa microparticles by analyzing the nano and ultrastructure properties giving rise to the different elasticities. We also establish feasibility for entrapping model hydrophobic drug, dexamethasone nanocrystals, and compare in-vitro release rates to that of free, non-entrapped drug to test the hypothesis that the microparticles will not have an effect on release. Ultrastructure of monodisperse, 12 μm particles of both soft and stiff formulations was investigated using cryo-scanning electron microscopy. To determine the effective permeability of the hydrogel polymer network, a size exclusion assay with varying sizes of FITC-dextran was performed. Confocal microscopy was used to visualize the fluorescent molecule permeation into the hyper-compliant microparticles. Release experiments used microparticles in which the water in the prepolymer solution was substituted with a sonicated suspension of dexamethasone. Aliquots from release media were taken at predetermined time points and analyzed over 96 hours for their drug concentration. Microparticles featured non-interconnected pores, with the 0.25 kPa formulation exhibiting significantly smaller pore size diameters and thinner polymer pore walls than the 10 kPa particles. Dextran size exclusion studies indicated that the soft hydrogel’s maximum effective permeability was 22 nm, more than double that of the stiff hydrogel’s network. This allows larger nanocrystals to be retained in the network, and only solubilized drug to diffuse out. Free dexamethasone exhibited a slightly faster dissolution than entrapped drug within the first four hours, but the overall release profile was not substantially different. These findings show that hydrophobic drugs can be entrapped in hyper-compliant microparticles without disrupting their structure or elasticity. Furthermore, because the microparticles do not hinder release, drug-entrapped nanoparticles for controlled, long-term delivery could be carried in the microparticles to avoid physiological filtration methods.
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