Tunable and sustained drug delivery platforms have great unmet potential to be used for more optimal treatment of human disease. Such delivery devices avoid bolus delivery and its undesirable systemic effects and toxicity. Controlled release can also overcome issues related to insufficient local concentrations of drug for the required timeframe since a single injection of naked drug can result in rapid degradation and subsequent distribution throughout the body. Microspheres offer one route for sustained and controlled release that have great potential as ideal platforms to deliver drugs in an optimized, sustained pattern. Many hydrolytically biodegradable microspheres have been pursued (i.e., PLGA). The focus of this thesis work has been on utilization of smart, stimuli-responsive polymers that release drugs at a rate dictated by the environment rather than hydrolytic degradation mechanisms that act independent of any environmental cues. For example, we have specifically sought applications for delivery to slightly acidic pH (5-7) tissues in cardiac ischemia and chronic diabetic wounds and to tissues laden
with cell-damaging reactive oxygen species (in particular hydrogen peroxide) such as in rheumatoid arthritis.
With this idea in mind, we formulated, characterized and studied in vitro release profiles of two novel types of smart, stimuli sensitive microspheres. These were pH and temperature-sensitive microspheres made from poly(NIPAAm-co-PAA-co-BA) (NPB microspheres), and Reactive Oxygen Species (ROS)-sensitive microspheres made from poly(propylene) sulfide (PPS microspheres). These intelligent microspheres demonstrated sustained release profile of encapsulated drugs when presented with ischemic pH and hydrogen peroxide as stimuli, indicating their potential for spatio-temporally controlled therapeutic delivery to ischemic and inflammatory environments, respectively. NPB microspheres formulated using a waterinoil-in-water double emulsion method were pursued specifically as candidates to encapsulate hydrophilic drugs (i.e. proteins). The PPS microspheres, on the other hand, were generated using a modified oil-in-water single emulsion method in order to pursue applications for delivery of more hydrophobic (i.e., small molecule) drugs.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12092011-155210 |
| Date | 12 December 2011 |
| Creators | Joshi, Rucha Vinay |
| Contributors | Dr. Hak-Joon Sung, Dr. Craig L. Duvall |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12092011-155210/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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