A robust regenerated cellulose-based dual stimuli-responsive hydrogel as an intelligent switch for controlled drug delivery

Constructing robust hydrogels with biodegradability and dual stimuli-responsive by utilizing natural polymer as raw materials remains a sustaining challenge. Herein, we proposed an interpenetrating strategy in which N-isopropyl acrylamide (NIPAM) and acrylamide (AM) block copolymers were introduced as the second network into the carboxymethyl cellulose single network gel (CMC gel) to construct a dual-network robust hydrogel (CMC/PNIPAM-co-PAM). The dual-network design strategy effectively improves the mechanical strength of CMC gel. The hydrogel suggests intelligent dual stimuli-responsive behavior to pH and temperature. Furthermore, the copolymerization of NIPAM and AM regulated the low critical solution temperature (LCST) of the hybrid hydrogel, making it close to the physiological temperature of the human body. With the aim of evaluating its application in drug delivery, we loaded tetracycline into the dual-network hydrogel and simulated its release process under the pH microenvironment of the small intestine and the physiological temperature to infer its potential application in intestinal inflammation treatments. Moreover, it is proved that the strong hydrogel possesses good cytocompatibility in vitro biocompatibility testing. In addition, the embedding of tetracycline makes the hydrogel excellent antioxidant performance. This dual-stimulus response integrated hydrogel is expected to play a critical role in drug delivery and targeted therapy.