THE SCHOOL OF MATERIALS SCIENCE AND ENGINEERING
GEORGIA INSTITUTE OF TECHNOLOGY
Under the provisions of the regulations for the degree
DOCTOR OF PHILOSOPHY
on Monday, July 2, 2018
in IBB Suddath Seminar Room 1128
will be held the
"Biopolymer Based Microneedle Patch for Polio Vaccination and Diagnostic Applications"
Prof. Mark Prausnitz, Advisor, ChBE
Prof. Valeria Milam, MSE
Prof. Vladimir Tsukruk, MSE
Prof. Sundaresan Jayaraman, MSE
Prof. Mostafa El-Sayed, CHEM/BioCHEM
The first half of this thesis is focused on the development of a dissolving microneedle (MN) patch for polio vaccination. Poliomyelitis (polio) is a highly infectious disease with no cure. Thus, the most effective strategy to eradicate polio is by vaccination. We developed a dissolving microneedle patch for administration of inactivated polio vaccine (IPV) with improved thermal stability when compared with commercial liquid IPV. A combination of maltodextrin, D-sorbitol and fish gelatin in histidine buffer was found to best preserve IPV activity during MN patch fabrication and storage. After 1 month at 40C, IPV activity was < 10 % for all three serotypes in a commercial liquid vaccine formulation but was > 40 % for all three serotypes in MN patches. In addition, activity remained >40% after 2 months and > 20% after 1 year of storage at 40C for all three IPV serotypes based on D-antigen content measured by ELISA. Residual moisture content in MN patches measured by thermogravimetric analysis, glass transition temperature measured by differential scanning calorimetry, structural changes measured by X-ray diffraction and molecular interactions measured by Fourier-transform infrared spectroscopy showed changes in MN matrix properties but did not correlate with IPV activity changes during storage. We conclude that appropriately formulated MN patches can exhibit thermostability that could enable distribution of IPV with less reliance on cold-chain storage.
The second half of the thesis is dedicated to the development of a simple MN patch for the collection of interstitial fluid (ISF) for diagnostic applications. ISF that surrounds cells in tissues of the body is a novel source of biomarkers similar to blood but relatively unexplored due to limitations in sampling techniques. To overcome difficulties in harvesting ISF, we developed a minimally invasive, rapid, simple-to-use and cost-effective method to collect ISF from the skin involving a MN patch. By pressing 750 µm long MNs at an angle just below the skin surface, blood-free ISF flowed through micropores to the skin surface and was absorbed into a thin strip of paper on the MN patch backing for subsequent analysis. An optimized method in rat skin in vivo was well tolerated and able to collect > 2 µl of ISF within 1 min. Brief skin pre-treatment with MNs followed by a 5 min delay dramatically increased subsequent ISF collection by a mechanism believed to involve increased skin hydration. We demonstrated the suitability of our MN patch for therapeutic drug monitoring in ISF by showing similar vancomycin concentration-time profiles and pharmacokinetic parameters in the ISF and blood in rat in-vivo. We also, for the first time, detected polio specific neutralizing antibodies, and anti-polio IgG in ISF similar to blood in rats immunized with the polio vaccine. ISF collection using a MN patch has the potential to simplify access to biomarkers in ISF for research and future immunodiagnostic and monitoring applications.