Development of a lower intestine targeting mucoadhesive platform of oral drug delivery

dc.contributor.advisorWilliams, Robert O., 1956-en
dc.contributor.advisorMcConville, Jason Thomasen
dc.contributor.committeeMemberMcGinity, James Wen
dc.contributor.committeeMemberCombs, Alan Ben
dc.contributor.committeeMemberSuggs, Laura Jen
dc.creatorJang, Shih-Fanen
dc.date.accessioned2013-07-02T16:06:15Zen
dc.date.issued2013-05en
dc.date.submittedMay 2013en
dc.date.updated2013-07-02T16:06:16Zen
dc.descriptiontexten
dc.description.abstractOur goal was to develop a mucoadhesive, oral vaccination delivery platform designed to target Peyer’s patches at ileum. In order to achieve this, we prepared poly(methyl methacrylate) (PMMA) particles of various sizes using W/O/W emulsification solvent evaporation and surface polymerization methods. We then coated and employed mucoadhesive polymers into the carrier system to enhance the residence time in the targeted site. Also we developed our own in vitro mucoadhesion testing ramp as an evaluation tool. Finally, nano- and micro-structured particles were manufactured as two different oral vaccine delivery systems (Solid Lipid Nanoparticles, SLNs; and Protein Coated Microcrystals, PCMC). After the model antigen, bovine serum albumin (BSA) was loaded into the SLNs or PCMC; mucoadhesive polymers were then incorporated and formulated the mixture into pellets. The pellets were then layered with an enteric coating, which was composed of a mixture of Eudragit® FS 30 D/Eudragit® L 30 D-55 for ileum targeted delivery. The in vitro mucoadhesion test ramp was capable of investigating the mucoadhesive properties of tablets and pellets, providing a rank order for study. Most important of all, it was anticipated that this might reduce the burden of testing animals for future proposed mucoadhesive studies. Microcapsules/beads of specific size were manufactured reproducibly by solvent evaporation and surface polymerization. Although we could not specify the cut-off size at the pyloric sphincter in mice, we concluded that the cut-off size at the pyloric sphincter in rats was approximately 2.5-3 mm, which was supported by both the biodistribution data and the direct image results from scintigraphy scanning. Moreover, we found that the particle size significantly alters the gastric emptying time in both rodent models. The small microcapsules/beads were hindered in the folds of the stomach (size 50-100μm for mice and size 0.5-1 mm for rats) and emptied the slowest, followed by the large particles, then the medium particles. Finally, PCMC and SLNs we manufactured were suitable carriers for protein API, such as BSA. These particles were of fitting size for M cell uptake, which would possibly induce mucosal immune responses. Therefore, an antigen containing PCMC and SLNs might be suitable platforms for oral vaccination.en
dc.description.departmentPharmaceutical Sciencesen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/20641en
dc.language.isoen_USen
dc.subjectOral vaccineen
dc.subjectProtein coated microcrystalsen
dc.subjectSolid lipid nanoparticlesen
dc.subjectMucoadhesionen
dc.subjectGastric cut-offen
dc.subjectGamma scintigraphyen
dc.titleDevelopment of a lower intestine targeting mucoadhesive platform of oral drug deliveryen
thesis.degree.departmentPharmacyen
thesis.degree.disciplinePharmacyen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen
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