Charged therapeutics such as nucleic acids and proteins can treat a vast range of human diseases that are traditionally undruggable. Their broadness in treating disease is due to their ability to influence cellular function. However, their high charge density and physiological barriers such as enzymatic degradation, hinder the deliverability of these molecules to the sites of disease. Polyelectrolyte complex (PEC) micelles are core-corona nanostructures that can encapsulate charged molecules and offer a platform for delivery. PECs form the core, when two oppositely charged polyelectrolytes are mixed in an aqueous solution, and the micelle corona is a neutral hydrophilic polymer that is conjugated to either one or both polyelectrolytes. The core promotes the encapsulation of charged therapeutics, while the corona offers protection, biocompatibility, and can be decorated with targeting ligands for improved bioavailability. PEC micelles can be highly tunable systems, allowing for features such as on-demand release capabilities to be engineered by altering the corona or core properties. In the first part of the dissertation, we use a thermoresponsive polymer to change the corona properties and study the structural changes at a physiologically hyperthermic temperature using dynamic light scattering (DLS) and small-angle x-ray scattering (SAXS). The structural changes were a function of the composition of the corona, with severe structural loss with a fully thermoresponsive corona and a preserved structure within larger aggregates for a partially thermoresponsive corona. Understanding the encapsulation capabilities and the effect of the PEC core properties on the micellar shape and size is of fundamental significance to the design of these micelles as drug delivery carriers. Using several physiochemical characterization techniques such as optical microscopy, fluorescence spectroscopy, DLS, SAXS, Förster resonance energy transfer (FRET) and transmission electron microscopy (TEM), we determined fundamental properties affecting the encapsulation capabilities and studied the structural changes and molecular dynamics of PEC micelles.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-1927 |
| Date | 01 December 2021 |
| Creators | Shah, Sachit |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
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