|dc.contributor.advisor||Peppas, Nicholas A., 1948-||en
|dc.creator||Wood, Kristy Marie||en
|dc.description.abstract||A novel class of pH sensitive complexation hydrogels composed of methacrylic
acid and functionalized poly(ethylene glycol) tethers, referred to as P(MAA-g-EG)
WGA, was investigated as an oral protein delivery system. The PEG tethers
were functionalized with wheat germ agglutinin (WGA), a lectin that can bind to
carbohydrates in the intestinal mucosa, to improve residence time of the carrier
and absorption of the drug at the delivery site.
P(MAA-g-EG) WGA created a specific mucoadhesive interaction between mucin
and WGA in in vitro experiments. In addition, it improved the overall adhesion of
the carrier by 17% to a cellular monolayer, as compared to P(MAA-g-EG).
Administration of P(MAA-g-EG) WGA to a rat small intestine demonstrated that
99% of the microparticles still remained in the rat small intestine after 1 hour.
These results confirmed that functionalizing P(MAA-g-EG) with WGA improved
the mucoadhesive properties of the carrier.
Insulin was effectively entrapped within the polymer network with a loading
efficiency of 74%. Release studies with insulin-loaded P(MAA-g-EG) WGA
showed that the carrier released less than 10% of the insulin at pH 3.2 after 60
minutes and 70% of the insulin at pH 7.0 after 60 minutes. These studies
confirmed that P(MAA-g-EG) WGA can protect insulin in the low pH of the
stomach and that the pH change between the stomach and the small intestine
can be used as a physiologic trigger to quickly release insulin.
The ability of P(MAA-g-EG) WGA to improve insulin absorption was investigated
in two different intestinal epithelial models and an animal model. In the Caco-2
cells, P(MAA-g-EG) WGA improved insulin permeability by 9-fold as compared to
an insulin only solution. P(MAA-g-EG) WGA was also evaluated in a mucussecreting
culture that contained Caco-2 and HT29-MTX cells. Insulin
permeability was increased by 5-fold in the presence of P(MAA-g-EG) WGA.
The final study determined bioavailability of insulin-loaded P(MAA-g-EG) WGA
when administered to a rat small intestine. Bioavailability of insulin was 11.9%
for insulin-loaded P(MAA-g-EG) WGA, which is a vast improvement over the
0.5% bioavailability of an insulin only solution. Overall, it is clear that P(MAA-gEG)
WGA holds great promise as an oral insulin delivery system.||
|dc.rights||Copyright is held by the author. Presentation of this material on
the Libraries' web site by University Libraries, The University of Texas at Austin was made
possible under a limited license grant from the author who has retained all copyrights in
|dc.subject.lcsh||Drug delivery systems||en
|dc.subject.lcsh||Colloids in medicine||en
|dc.title||Molecular design of advanced oral protein delivery systems using complexation hydrogels||en