Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/18303
Title: | Synthesis and Applications of Degradable Thermoresponsive Microgels |
Other Titles: | Synthesis of Degradable Thermoresponsive Microgels |
Authors: | Sivakumaran, Daryl N |
Advisor: | Hoare, Todd |
Department: | Chemical Engineering |
Keywords: | Microgels;Nanocomposite Hydrogels;Drug Delivery;Microfluidics;Self-assembly;Degradability;Enviromentally-responsive |
Publication Date: | Nov-2015 |
Abstract: | Microgels are solvent-swollen cross-linked gel particles with sub-micron diameters and have been widely investigated for drug delivery applications. Thermoresponsive microgels based on poly(N-isopropylacrylamide) (PNIPAM) have attracted particular attention given their potential to enable pulsatile or environment-specific drug release. However, current methods to make thermoresponsive microgels yield functionally non-degradable materials, significantly limiting their utility in vivo. Herein, hydrazone chemistry was applied to cross-link hydrazide and aldehyde-functionalized precursor polymers together to form degradable PNIPAM microgels on different length scales that enable potential use of thermoresponsive microgels in vivo in a way not currently possible. For micron-scale microgels, microfluidics was employed to create monodisperse microgels between 30-90 m. For nano-scale microgels, a temperature-driven aggregation/self-assembly technique was developed that resulted in the formation of microgels with sizes between 200-300 nm. In either case, the microgels can be slowly degraded through hydrazone hydrolysis. Functionalized microgels can be made by incorporating pH-responsive 2-dimethylaminoethylmethacrylate (DMAEMA) or glucose-responsive phenylboronic acid in the precursor polymers. The potential utility of degradable microgels in drug delivery was studied using in situ gelling microgel-hydrogel nanocomposites. Changing the microgel cross-link density and whether or not the microgels were physically entrapped or covalently cross-linked to the bulk hydrogel matrix resulted in significant changes in drug release kinetics, with burst release particularly mitigated by increasing the cross-link density of the microgels. Microgels made via microfluidics were then utilized to make fully degradable microgel-hydrogel composites consisting of chemically identical gel chemistries on both the bulk and micro length scales. Carbohydrates (carboxymethyl cellulose and dextran) and PNIPAM gel phases were oriented in different relative geometries to examine how the phase distribution impacted drug release. Results suggest that drug release can be controlled through the selection of polymer type of each phase, with the deswelling phase transitions of PNIPAM playing a particularly large role in slowing release of the drug. |
URI: | http://hdl.handle.net/11375/18303 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Sivakumaran_Daryl_N_2015Sept_PhD.pdf | PhD Thesis | 5.17 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.