Supersensitive Oxidation-Responsive Biodegradable PEG Hydrogels for Glucose-Triggered Insulin Delivery

Reactive oxygen species (ROS)-responsive polymers and hydrogels represent an emerging family of intelligent materials owing to the key functions of ROS in physiological processes or pathological diseases. Nonetheless, the weaknesses such as low sensitivity, slow response, instability, and low mechanical strength are associated with the limited ROS-responsive polymeric or supramolecular hydrogels. In this study, a novel type of oxidation-responsive degradable hydrogels was fabricated by the redox-initiated radical polymerization of a 4-arm-poly(ethylene glycol) (PEG) acrylic macromonomer that possesses a H 2 O 2 -cleavable phenylboronic acid linker in each of the arms. The macroscopic hydrogels have the features of good cytocompatibility, moderate mechanical strength, and fast response toward H 2 O 2 of low concentration, owing to the covalently cross-linked hydrophilic PEG network and high sensitivity of the linker. They could encapsulate biomacromolecules, such as insulin and glucose oxidase (GOx), with high efficacy, affording a new glucose-responsive insulin-delivery platform on the basis of enzymatic transformation of a biochemical signal (glucose) into an oxidative stimulus (H 2 O 2 ). Interestingly, in vitro results demonstrate that the same GOx-loaded hydrogel exhibited disparate degradation modes under different triggering molecules, that is, bulk degradation by H 2 O 2 and surface erosion by glucose. Moreover, compared to the macroscopic hydrogel, the nanogel with a diameter of ∼160 nm prepared by inverse emulsion polymerization showed a much higher degradation rate even under triggering of 20 μM H 2 O 2, a pathologically available concentration in vivo.