An injectable, dual pH and oxidation-responsive supramolecular hydrogel for controlled dual drug delivery

A novel pH and oxidation dual-responsive and injectable supramolecular hydrogel was developed, which was formed from multi-block copolymer poly(ether urethane) (PEU) and α-cyclodextrin (α-CD) inclusion complexes (ICs). The PEU copolymer was synthesized through a simple one-pot condensation polymerization of poly(ethylene glycol), di(1-hydroxyethylene) diselenide, dimethylolpropionic acid and 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate. In aqueous solution, the amphiphilic PEU copolymers could self-assemble into nanoparticles with dual pH and oxidation sensitivities, which can efficiently load and controllably release a hydrophobic drug indomethacin (IND). Then a dual-drug loaded supramolecular hydrogel was obtained by addition of α-CD and hydrophilic model drug (rhodamine B, RB) into the resulting IND-loaded PEU nanoparticle solution. The rheology studies showed that the supramolecular hydrogels with good injectability underwent a pH-induced reversible sol-gel transition and an oxidation-triggered degradation behavior. The in vitro drug release results demonstrated that the hydrogels showed dual drug release behavior and the release rates could be significantly accelerated by addition of an oxidizing agent (H2O2) or increasing the environmental pH. Therefore, this injectable and dual stimuli-responsive supramolecular hydrogel based codelivery systems could potentially be a promising candidate for controlled drug delivery systems.