Synthesizing Reactive Oxygen Species Sensitive Drug Delivery Vehicles



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Drug 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.



Reactive oxygen species, Drug delivery, Synthesis, Superoxide, Hydrogen peroxide, Triflate, Boronic ester, Dextran, Transesterification