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Title page for ETD etd-12092011-155210


Type of Document Master's Thesis
Author Joshi, Rucha Vinay
Author's Email Address rucha.v.joshi@vanderbilt.edu
URN etd-12092011-155210
Title Smart Microspheres for Stimuli Responsive Drug Delivery, W/O/W double emulsion method, O/W single emulsion method
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Dr. Craig L. Duvall Committee Chair
Dr. Hak-Joon Sung Committee Co-Chair
Keywords
  • LCST
  • ROS
  • temperature
  • pH
  • microspheres
  • stimuli responsive polymers
  • cumulative release
  • characterization of microspheres
  • PPS
Date of Defense 2011-12-06
Availability unrestricted
Abstract
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 water–in–oil-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.

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