Abstract:
This dissertation describes two different projects. The first is the development
of an oral DNA vaccine delivery system for fish. A novel oral DNA vaccine delivery
system was developed for Rainbow Trout by combining non-viral vectors
(polycationic liposomes or polycationic polymer) to facilitate the DNA vaccine's
uptake by cell membranes along with enteric-coated protection of the DNA embedded
in microparticles to prevent DNA degradation in the gastrointestinal tract. Spray
drying and spray coating bead techniques were employed in the preparation of the
DNA vaccine microparticles. The spray drying technique allowed production of
spherical shape enteric-coated microparticles with a particle size range of 0.18 to 20
μm. Larger particle sizes of 40-50 mesh were obtained from the spray-coated bead
technique. The resultant DNA vaccine microparticles were granulated with regular
fish feed and given to fish to investigate the efficacy of the delivery system in
providing protection against IHNV, and to demonstrate the ease of administration in
fish. An in vivo fish trial experiment showed improvement in fish survival rate when
fish were immunized with larger particle size DNA vaccine microparticles. Further
research to find effective vector carriers for the DNA vaccine delivery system and to
seek modifications of the delivery system that will still prevent the denaturation of
plasmid DNA that will also facilitate membrane uptake of the DNA vaccine is needed
in order to develop a safe, effective, and commercially viable vaccine to control the
outbreak of IHNV.
The second project of the dissertation is prediction of in vitro drug release
profiles from a novel matrix tablet spray-coated with a barrier membrane using
mathematical and statistical models. Tablets were prepared by direct compression
followed by spray coating. The relationship of the amount of hydrophilic materials in
the core tablets and barrier thickness on drug release mechanism was investigated
using factorial design and regression analysis. Drug release characteristics were
influenced and can be controlled by modifying the amount of hydrophilic materials in
the core tablet and the barrier thickness. Mathematical equation generated from
regression analysis of n-value, lag time, and percent drug release as a function of the
amount of hydrophilic material and the amount of coating material applied can now be
used as a tool for predicting and optimizing in vitro drug release from matrix tablets
spray-coated with a barrier membrane.
