Date of Graduation

5-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Julie A. Stenken

Committee Member

Ingrid Fritsch

Second Committee Member

Feng Wang

Third Committee Member

Robert H. Coridan

Fourth Committee Member

Shannon Servoss

Keywords

Microdialysis; NSAID; covalent organic frameworks

Abstract

Microdialysis is a valuable tool in neurosciences and pharmaceutical sciences, aiding research in drug-related areas. However, it faces a notable limitation in sampling hydrophobic analytes due to their adherence to the probe materials brought about by non-specific adsorption, thereby reducing relative recovery or overall extraction. In this work, two affinity agents, polydimethylsiloxane (PDMS) beads suspended in sodium dodecyl sulfate (SDS) surfactant and covalent organic frameworks I(COFs) were employed as affinity agents in microdialysis for the extraction of hydrophobic drugs. When PDMS beads were employed as affinity agents, at the flow rate of 1 µL/min the relative recovery of both the control and affinity agent statistically significantly increased from 35.46 ± 3.20% and 49.42 ± 2.04% to 72.41 ± 2.42% and 100.29 ± 2.85% respectively when the membrane length was increased from 4 mm to 10 mm. While SDS was effective in stabilizing the PDMS emulsions during synthesis, its cytotoxic properties pose a significant barrier to the translation of this technology for in vivo studies. This drawback necessitates the exploration of alternative, biocompatible surfactants that can perform the required role without compromising cellular health. Three distinct imine-based COFs (COF-UARK-49, TPEDDA COF, TPBD COF) with varying characteristics—shape, surface area, pore sizes, and pore volumes—were employed to enhance microdialysis relative recovery of three NSAIDs (flurbiprofen, naproxen, fenbufen) and two metabolites (4-hydroxy flurbiprofen, 4-biphenyl acetic acid) with log P (octanol-water partition coefficient) values ranging from 3.0 to 4.2. These COFs were selected for their structural regularity, high crystallinity, and chemical stability in both organic solvents and water. The results indicate substantial relative recovery enhancements, ranging from 2- to 15-fold increments, COF-UARK-49 exhibited the highest relative recovery, followed by TPEDDA and TPBD, aligning with their surface area, pore size, and pore volume characteristics. This study highlights the potential of COFs as a promising tool for the enhancement of relative recovery of hydrophobic drugs using the microdialysis technique, furthermore, the relative recovery enhancement observed is a function of the surface area of individual COF types and other characteristics specific to the COF.

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