Control of Glucose‐Induced Degradation and Cargo Release in Multi‐Responsive Polymer Hydrogels

Abstract On‐demand cargo/drug release from hydrogel under physiological conditions is a significant challenge for advanced therapeutics. Specifically, smart hydrogels capable of the glucose‐responsive release of anti‐diabetic drugs are of current research thurst. Despite the recent developments, there is a need for more glucose‐sensing hydrogel that retain the properties in a wide‐range of pH environments. Herein, a facile and generalized fabrication strategy of multiple stimuli (pH, glucose, and hydrogen peroxide)‐responsive hydrogels is reported. Poly(vinyl alcohol) (PVA) is crosslinked with three bis‐boronic acid molecules‐ benzene‐1,4‐diboronic acid (1,4‐BDBA), 4,4′‐biphenyldiboronic acid (4,4′‐BPDBA), tetrahydroxydiboron(THDB) in ambient conditions to produce hydrogels with water content > 80% and suitable for (macro)molecular cargo incorporation in the matrix. Extensive analytical studies suggest that hydrogels derived from 1,4‐BDBA and 4,4′‐BPDBA show degradation under the stimuli mentioned earlier, but THDB crosslinked hydrogel does not degrade under pH or glucose environment. This unusual property allows the incorporation of glucose oxidase (GOx) in the hydrogel matrix that imparts the glucose responsiveness for THDB crosslinked hydrogel. Finally, the glucose‐specific release of (macro)molecular cargo/drugs is demonstrated in a glucose oxidase containing PVA/THDB hydrogel in the physiological milieu. The hydrogel developed herein will open up new ways to develop glucose‐specific smart‐matrix for the on‐demand delivery of drugs.