(27bs) Glutathione-Responsive Disulfide-Containing Poly (?-amino esters) Nanogels for Drug Delivery Applications

Oxidative stress is a ubiquitous pathophysiological process that occurs in concert with the inflammatory pathway. During this process, highly reactive free radicals partake in a series of chemical reactions with cellular components and biomolecules, substantially damaging them, and further affecting the function of tissues as organs. Glutathione (GSH) is a tripeptide that plays a critical role in scavenging and neutralizing free radicals and serves as a cofactor for multiple enzymatic systems. Commonly found in the cytosol, GSH also serves as a thiol buffer maintaining sulfhydryl groups of many biomolecules in their reduced form. We have previously developed disulfide-containing PBAEs as a means of regulating and responding to oxidative stress. However, while these materials were shown to serve as a protective agent, we have not evaluated the direct interaction of these materials with GSH. In this work, we developed novel disulfide PBAE nanogels that are sensitive to physiological levels of glutathione (GSH), a key component in the regulation of cellular oxidative stress, and can be used to achieve tunable release in the presence of varying GSH concentrations.