Open Access Thesis
Date of Award
HDAC inhibitors are known to have anti-inflammatory properties. HDAC inhibitors are used in combination with Oct4 to generate induced pluripotent stem cells. I hypothesized that polyesters based on simple aliphatic HDAC inhibitors like valproic acid (VPA) and phenylbutyric acid (PBA) can serve as alternatives to existing polyester biomaterials with improved anti-inflammatory properties and as scaffolds for generation of iPSCs when used in combination with layer-by-layer thin films delivering reprogramming transcription factors. Vinyl ester of phenylbutyric acid (VEPA) and vinyl ester of valproic acid (VEVA) were synthesized from their carboxylic acid precursors using an iridium complex catalyst at yields as high as 97% and 73%, respectively. Amorphous poly(VEPA) and poly(VEVA) polymers were prepared by free radical solution polymerization and characterized for molecular weight and glass transition temperature. Poly(VEPA) and poly(VEVA) microparticles of 20-40 um diameter were prepared by an emulsion-solvent evaporation method and examined under scanning electron microscopy (SEM). Their hydrolytic degradation was studied by dry weight loss and HDAC inhibitor release via high performance liquid chromatography (HPLC) in the presence of varied pH and lipase-containing buffers. No significant degradation occurred within 5 days, and an MTT assay conducted on HeLa cells in the presence of these microparticles confirmed an absence of cytotoxicity. Poly(VEPA) and poly(VEVA) microparticles were not found to be a suitable biomaterial for hypothesized applications in light of their poor degradation characteristics in vitro.
Horton, Kyle Lawrence, "Synthesis And Characterization Of Biodegradable Poly(vinyl Esters) With Hdac Inhibitory Activity" (2013). Wayne State University Theses. 234.