Smart Hydrogels Co-switched by Hydrogen Bonds and π-π Stacking for Continuously Regulated Controlled-Release System

A series of hydrogels with continuously regulatable release behavior can be achieved by incorporating hydrogen bonding and pi-pi stacking co-switches in polymers. A poly(nitrophenyl methacrylate-co-methacrylic acid) hydrogel (NPMAAHG) for control over drug release is fabricated by copolymerizing 4-nitrophenyl methacrylate and methacrylic acid using ethylene glycol dimethacrylate as a crosslinker. The carboxylic acid groups and nitrylphenyl groups form hydrogen bonds and pi-pi stacking interactions, respectively, which act as switches to control the release of guest molecules from the polymers. As revealed by the simulated gastrointestinal tract drug release experiments, the as-synthesized NPMAAHG hydrogels can be regulated to release only 4.7% of drugs after 3 h in a simulated stomach and nearly 92.6% within 43 h in the whole digestive tract. The relation between the release kinetics and structures and the mechanism of the smart release control are analyzed in terms of diffusion exponent, swelling interface number, drug diffusion coefficient, and velocity of the swelling interface in detail. The results reveal that the release of guest molecules from the hydrogels can be continuously regulated for systemic administration by controlling the ratio of the hydrophilic hydrogen bonds and the hydrophobic pi-pi stacking switches.