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Dissertation
Determination of the in vitro and in vivo oral drug delivery capabilities of complexation hydrogels
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2006
DOI:
https://doi.org/10.17918/etd-1305
Abstract
The promise of oral delivery formulations of therapeutic protein and peptides is one of high hopes but also of disappointment as, to date, parenteral administration remains the standard of care. A good example of this is in the case of human insulin delivery for diabetes where disease control, reduction of degenerative side effects and increased patient compliance could all be gained in the most rapidly growing disease in our country. Hydrogel carrier systems have shown promise as a potential solution for this unmet medical need. In particular a novel pH-sensitive poly[methacrylic acid-grafted-poly(ethylene glycol)] hydrogel system has shown promise by displaying enhanced insulin delivery in in situ animal models. In this work, a set of detailed in vitro and in vivo experiments were used to further qualify the insulin delivery capabilities of this novel system. The ability of the system to protect entrapped insulin in the upper gastrointestinal tract was confirmed via dissolution studies and the ability of the polymer system to enhance transport across the intetinal epithelium was confirmed using the Caco-2 in vitro model of intestinal transport. Lastly, the absolute oral bioavailability of insulin delivered via the hydrogel system was determined in rats and dogs. The application of pharmacokinetic models to the animal data shows the greatest gains on improving this delivery system can be made by optimizing the ability of the hydrogel to enhance protein transport across the gut wall.
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Details
- Title
- Determination of the in vitro and in vivo oral drug delivery capabilities of complexation hydrogels
- Creators
- Eric D. Perakslis - 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
- 1305; 991014632246604721