van Giessen, AlanBalasubramanian, SuprajaBroaders, KylePollock-O'Dorisio, Natalia2025-07-152025-07-152025-07-15https://hdl.handle.net/10166/6768This work explores modified dextran as a drug delivery system from two angles. The first aims to provide an in-depth structural characterization of substitution affinity and heterogeneity of Ac-Dex. The second is an exploration of novel triggers to create an H2S sensitive solubility switching material. This work aims to provide two perspectives into methods of optimization of drug delivery systems based on the polysaccharide dextran. Acetal-modified dextran (Ac-Dex) is a solubility switching polymer. Historically it has been used to form nanoparticles which can encapsulate drugs for targeted release vaccine delivery. It is insoluble in water, but under acidic conditions the acetals hydrolyze, converting it into water soluble dextran. Ac-Dex is prepared through modification of dextran with 2-methoxypropene, generating a heterogeneously modified polymer. Each monomer subunit in dextran has three possible hydroxyls for modification; additionally, the acetals can be either cyclic or linear, meaning there are 12 different possible modifications per monomer. The different types of modification affect the degradation rate of the polymer. It would be ideal to understand the conditions that favor each type of modification so that a more homogenous polymer can be synthesized consistently. This study details the synthesis and use of 1,6-dimethyl glucose for use as a monomeric model compound for dextran, in which the methyl caps simulate the glycosidic bonds of a dextran backbone. We report here on progress toward measuring and synthetically controlling the distribution of acetal modifications on dextran in the formation of Ac-Dex. Modified dextran as a solubility switching polymer has shown promise with a variety of capping mechanisms. H2S has been found to act as a gasseotransmitter within the body. As such it is subject to upregulation in the body in response to certain disease states. It would be desirable to have a targeted delivery method available for H2S associated diseases. In an effort to create an H2S triggered solubility switching polymer based on dextran, an aryl azide was selected as a capping group. This group has shown efficacy in H2S sensing fluorophores and was therefore adopted as a capping group on dextran. This body of work reports on the synthesis and characterization of such a material, as well as its prospects for further adoption.en-USModified DextranSolubility Switching MaterialsDrug DeliveryThesispublic