Stimuli responsive hydrogels are useful platforms for the encapsulation and controlled release of proteins where light responsive chemistries are a powerful tool for tuning the rate of protein release to achieve on-demand release profiles. Nitrobenzyl (NB) linkers are commonly incorporated within hydrogels to impart light responsive properties owing to their ability to degrade in response to cytocompatible doses of light; however, the nature of the photolabile bond and its context have been observed to lead to variability in the rate of photodegradation and hydrolysis of the linker. For example, the behavior of NB groups within the aqueous and confined environment of hydrogels has been observed to be different than that observed with small molecules in free solution. Additionally, the different behavior between the two most frequently used NB groups within hydrogels, photolabile ester or amide linkers, is not well understood impacting the broad utility of these linkers for therapeutic applications. This work addresses these concerns by characterizing the rates of photodegradation and hydrolysis for ester, amide, carbonate, and carbamate-linked NB-containing hydrogels. Specifically, bioinert poly(ethylene glycol) (PEG) hydrogels were formed integrating photolabile crosslinks that contained the various photocleavable bonds. Hydrogel degradation was examined by monitoring mechanical properties and swelling over time upon light exposure or under accelerated hydrolysis conditions. Notably, the carbamate-linked NB group was found to have a fast photodegradation rate combined with long term stability in aqueous environments, making it a good candidate for protein delivery applications where complete temporal control over protein release with light is desired. To demonstrate the utility of using the different NB groups to control protein release, hydrogels containing layers formed with different, complementary linkers were fabricated. Specifically, two layers were formed as concentric cylinders, one layer containing the ester-linked NB crosslinker and the other the carbamate-linked NB crosslinker for rapid hydrolysis followed by photolysis. With this approach, unique release profiles were achieved with model cargoes of relevance for the controlled release of proteins. By understating the degradation behavior of NB linkers within hydrogels, protein delivery platforms with controlled and tunable properties can be designed towards personalized medicine applications.

Photodegradable hydrogels for protein delivery: Tuning degradation rates through cleavage bond chemistry

2019 Spring National Meeting

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