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Dissertation
Analysis and novel characterization of synthetic and biologically enhanced complexation hydrogels for oral protein delivery
Doctor of Philosophy (Ph.D.), Drexel University
2011
DOI:
https://doi.org/10.17918/etd-3644
Abstract
Graft copolymer networks have shown promise as devices for oral delivery of proteins. By increasing adhesion of these networks at the delivery site of the upper small intestine by utilizing small chemical linkages caused by the novel addition of a synthetic or biological functional groups we can make them more viable. The synthetically functionalized aldehydes bind covalently by way of a condensation reaction with the amines of the amino acids found in the glycoprotein network of the mucus layer of the small intestine to form imines. The biologically grafted SlpA protein adhesin from L. acidophilus binds to human epithelial cells, mucus and fibronectin. To investigate the effectiveness of these bonds, P(MAA-EG) copolymers are prepared with varying percentages of grafted aldehyde modified PEG or SlpA protein adhesin and characterized. When swollen in buffered solution, results indicate that all formulations with the aldehyde modified PEG or SlpA protein adhesin maintained the desired pH sensitivity and transition as those formulations without modification. Bulk adhesion testing was carried out through the use of a mechanical testing apparatus for aldehyde modified hydrogels in contact with mucus. Adhesion results show an increase to the already present adhesion of the copolymers due to increased percentages of the aldehyde modified PEG tethers where the highest modified formulation had the largest increase over both control formulations. Molecular adhesion testing was performed on the aldehyde modified hydrogels utilizing atomic force microscopy as a novel in vitro testing method. The new method was developed to gauge the intricacies of adhesion. After, using a new technique to build hydrogel capped AFM testing tips, experiments wereperformed with mucus with results indicating an overall increase of adhesion across all formulations when compared to bulk tensile testing. Bulk adhesion testing for the SlpA modified hydrogels with Caco-2 cells also showed an increase to the already present adhesion of the control copolymers.
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Details
- Title
- Analysis and novel characterization of synthetic and biologically enhanced complexation hydrogels for oral protein delivery
- Creators
- F. Michael Marks III - DU
- Contributors
- Anthony M. Lowman (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Chemical (and Biological) Engineering [Historical]; College of Engineering (1970-2026); Drexel University
- Other Identifier
- 3644; 991014632169204721