Abstract:
Current polymer-based nanomedicine carriers used in chemotherapy have several shortcomings regarding their efficacy: low drug loading capacity, premature drug release, poor in vivo monitoring capability, and limited accumulation in the targeted region. To address these shortcomings, my research investigates the use of disulfide-containing polymeric prodrug carriers. These polymer carriers self-assemble around the drug, encapsulating it, but contain disulfide cleavage links, which are cleaved and release cargo when glutathione (GSH) concentrations, a characteristic of the tumor microenvironment, is elevated. Two experimental carriers were synthesized: the cystamine carrier and the R848 carrier. Cysteamine is a linear compound containing both amine and thiol groups, so designing a carrier capable of binding to cysteamine demonstrates its ability to bind other drug targets with similar properties. Additionally, R848 is a cyclic compound containing both amine and hydroxyl groups, so designing a carrier capable of binding to R848 demonstrates its ability to bind other drug targets with similar properties. Preliminary results regarding reaction purity and efficacy have been promising. 1H-NMR spectra for each synthesis step have shown high purity, confirming the reaction and purification methods used. The reaction yields for the first three steps of the homocysteine projects were 62.7%, 58.7%, and 37.7%, respectively. The reaction yield for the first step of the terephthalic acid project was 22%. Although some of the yield values are relatively low, when paired with the 1H-NMR spectra, the results suggest that with minor modifications, the purity and efficiency of the reactions could be improved.
