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Dissertation
Development and characterization of a novel metal ion binding-mediated drug delivery mechanism for biomedical applications
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2015
DOI:
https://doi.org/10.17918/etd-7581
Abstract
Minocycline hydrochloride (MH) is a tetracycline derivative antibiotic that also has anti-inflammatory, anti-oxidative, and anti-apoptotic properties. It has demonstrated therapeutic effects in infection, inflammation, tumor, as well as cardiovascular, renal, and neurological disorders due to its anti-microbial, anti-inflammatory, and cytoprotective properties. However, the inability to translate the high doses used in experimental animals to tolerable doses in human patients limits its clinical application. Localized delivery can potentially expose the diseased tissue to high concentrations of MH that systemic delivery cannot achieve, while minimizing the side effects from systemic exposure. However, current drug delivery systems are not ideal for local delivery of bioactive MH for an extended period of time because it is a small molecule drug (MW 494 Da) with high water solubility. In this study, we developed a novel metal ion binding mediated drug delivery mechanism. Based on this mechanism, we developed two drug delivery systems: layer-by-layer (LbL) thin film coatings and self-assembled insoluble complex. In addition, the interaction between MH and dextran sulfate (DS), as well as the factors affecting MH release were studied. Moreover, the complexes can be encapsulated into an injectable agarose hydrogel to be immobilized at the injury site. We also investigated strategies to control MH release from the hydrogel. Furthermore, we investigated using the metal ion-assisted self-assembled complex for controlled and sustained delivery of therapeutic proteins for biomedical applications.
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Details
- Title
- Development and characterization of a novel metal ion binding-mediated drug delivery mechanism for biomedical applications
- Creators
- Zhiling Zhang - DU
- Contributors
- Yinghui Zhong (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 170 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 7581; 991014632175604721