Polysaccharide decoration of complexation hydrogel networks for oral protein delivery

dc.contributor.advisorPeppas, Nicholas A., 1948-en
dc.contributor.committeeMemberMaynard, Jenniferen
dc.contributor.committeeMemberRoy, Krishnenduen
dc.contributor.committeeMemberRylander, H G.en
dc.contributor.committeeMemberSchmidt, Christineen
dc.creatorPhillips, Margaret Annen
dc.date.accessioned2011-10-12T15:16:49Zen
dc.date.available2011-10-12T15:16:49Zen
dc.date.issued2011-08en
dc.date.submittedAugust 2011en
dc.date.updated2011-10-12T15:17:23Zen
dc.descriptiontexten
dc.description.abstractPolysaccharide-decorated complexation hydrogels were investigated for use as oral insulin delivery systems. Several different polysaccharide modifications of poly(methacrylic acid-grafted-ethylene glycol) hydrogels were developed using dextran and pullulan. Polymerizable groups were added to the polysaccharides, dextran and pullulan, by methacrylation. These macromers were then copolymerized with methacrylic and poly(ethylene glycol) to form P(MAA-g-EG-co-Dextran) and P(MAA-g-EG-co-Pullulan) gels using a UV-initiated free radical polymerization. The synthesis of these materials was confirmed using Fourier transform-infrared spectroscopy. The pH-responsive swelling of these systems was investigated using dynamic and equilibrium swelling measurements. Swelling of polysaccharide-modified hydrogels occurred with increasing pH. In acidic conditions, these materials were in a collapsed state while in neutral conditions these materials were swollen. The ability to load insulin into these hydrogels using was demonstrated with loading efficiencies as high as 88% were observed for P(MAA-g-EG-co-Dextran 6000) hydrogel microparticles. Almost zero release of insulin occurred in acidic conditions while an increase in pH was shown to trigger release. The use of dextran and pullulan-modified complexation hydrogels for oral delivery applications was investigated using in vitro cellular viability assays and mucoadhesion experiments. These systems were shown to cause little cytotoxicity to an intestinal epithelium Caco-2 cell model over a range of concentrations as high as 1 mg/ml. The adherence of polysaccharide-modified hydrogels to reconstitituted mucin gels was quantified with the P(MAA-g-EG-co-Dextran 6000) performing the best. Further evaluation of polysaccharide-modified complexation hydrogels for oral insulin delivery was evaluated through in vitro insulin drug transport studies using a mucus-producing Caco-2/HT29-MTX co-culture model. The results showed that the P(MAA-g-EG-co-Dextran 6000) allowed transport of insulin across the cell monolayers and did not adversely affect the integrity of the epithelial monolayer.en
dc.description.departmentBiomedical Engineeringen
dc.format.mimetypeapplication/pdfen
dc.identifier.slug2152/ETD-UT-2011-08-3746en
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2011-08-3746en
dc.language.isoengen
dc.subjectHydrogelsen
dc.subjectOral protein deliveryen
dc.subjectCarbohydratesen
dc.subjectMucoadhesive hydrogelsen
dc.titlePolysaccharide decoration of complexation hydrogel networks for oral protein deliveryen
dc.type.genrethesisen
thesis.degree.departmentBiomedical Engineeringen
thesis.degree.disciplineBiomedical Engineeringen
thesis.degree.grantorUniversity of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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