Synthesizing Reactive Oxygen Species Sensitive Drug Delivery Vehicles

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dc.contributorMcMenimen, Kathryn
dc.contributorChumley, Timothy
dc.contributor.advisorBroaders, Kyle
dc.contributor.authorHaskell, Isabela
dc.date.accessioned2023-06-30T14:20:19Z
dc.date.available2023-06-30T14:20:19Z
dc.date.gradyear2023en_US
dc.date.issued2023-06-30
dc.description.abstractDrug delivery vehicles can be designed to provide a more efficient and effective tactic for delivering therapeutic payloads to their sites of activity by protecting their cargo until degradation conditions are met. Because of the association between high concentrations of reactive oxygen species with a variety of inflammatory diseases, the reactive oxygen species superoxide and hydrogen peroxide are appealing targets for payload release. The compound trifluoromethyl sulfonate has been found to degrade in the presence of superoxide (Chen, et al. 2019). Modification of dextran polymer with trifluoromethyl sulfonate is expected to confer hydrophobicity to the polymeric material and exposure to superoxide reverts it back to a hydrophilic material. The hydrophobic-modified dextran will form nanoparticles upon precipitation into an aqueous solvent. However, characterization by proton NMR and apparent solubility suggests that improvements need to be made in future synthesis, as the modification was unsuccessful. Boronic esters have been widely used to trigger degradation in the presence of hydrogen peroxide, and pinacol is an especially common esterifying diol used (Broaders, et al. 2011). Recent studies have found that dextran polymer-based delivery vehicles modified with pinanediol, a rigid diol, are more stable and soluble in organic solvents than their pinacol counterparts (Manaster, et al. 2019). Pinacol delivery vehicles (Pin-B Dex) can be made multifunctional through the addition of diols conjugated to therapeutic or fluorescent molecules via boronic ester transesterification reactions. Pinacol was successfully added to dextran, confirmed by H-NMR, and addition of pinanediol confirmed that Pin-B-Dex can be modified. In order to add more functional modifications, fluorescence, or therapeutic molecules, the modification molecule of choice will be attached to nopol diol enabling its addition onto Pin-B Dex. One such modification was synthesized through the addition of pyrenebutyric acid, a fluorescent molecule, onto nopol diol. Pin-B-Dex was successfully modified according to H-NMR; however, the small yield of the product suggests that improvements could be made in future syntheses.en_US
dc.description.sponsorshipBiochemistryen_US
dc.identifier.urihttp://hdl.handle.net/10166/6437
dc.language.isoen_USen_US
dc.rights.restrictedrestricteden_US
dc.subjectReactive oxygen speciesen_US
dc.subjectDrug deliveryen_US
dc.subjectSynthesisen_US
dc.subjectSuperoxideen_US
dc.subjectHydrogen peroxideen_US
dc.subjectTriflateen_US
dc.subjectBoronic esteren_US
dc.subjectDextranen_US
dc.subjectTransesterificationen_US
dc.titleSynthesizing Reactive Oxygen Species Sensitive Drug Delivery Vehiclesen_US
dc.typeThesis
mhc.degreeUndergraduateen_US
mhc.institutionMount Holyoke College

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