Non-Hydrolysable Oxanorbornadiene Hydrogels with retro-Diels-Alder Programmed Degradation
Author(s)
Goli, Jagruti
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Abstract
Injectable hydrogels have shown their potential for the development of stable-release drug delivery platforms used to reduce the frequency of injections. We are exploring a novel system using the Michael addition between dextran functionalized with Oxanorbornadiene (OND) electrophiles and polyethylene glycol terminated with thiol nucleophiles. The resulting hydrogels demonstrate programmable release rates and profiles, ranging from minutes to several months, that depend on a combination of two cleavage reactions: ester bond hydrolysis and retro-Diels-Alder (rDA) reaction of OND-thiol adducts. This study investigates the consequences of replacing the hydrolysable ester linkages with stable amide bonds made between the ONDs and dextran-carboxylates, starting with the optimization of the synthesis of OND-dextran with amide linkages. The synthetic scheme for OND-dextran was optimized to use 40 eq OND-amine and 4-dimethylaminopyridine (DMAP) to lower the activation energy for amide coupling, obtaining a final 9%DS. Degradation of these injectable materials is controlled solely by the rDA process, improving predictability, capacity, and programmability of payload release.
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2026-05
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Undergraduate Thesis