pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan for localized drug delivery

Injectable hydrogels with multifunctional properties, including tissue adhesiveness and pH-sensitivity are highly desired for localized drug delivery in disease treatment, and their design is still challenging. We developed a series of multifunctional injectable mucoadhesive and pH-responsive hydrogels based on chitosan-grafted-dihydrocaffeic acid (CS-DA) and oxidized pullulan (OP) via a Schiff base reaction. These hydrogels exhibited good injectability, suitable gelation time, in vitro pH-dependent equilibrated swelling ratios, morphologies, and rheological characteristics. The desirable in vitro pH-sensitive drug release behavior of these hydrogels was demonstrated by a drug release test with anti-cancer drug doxorubicin (DOX) loaded hydrogels at different pH values. The hydrogels showed good DOX release, effectively killing colon tumor cells (HCT116 cells) and good antibacterial properties against E. coli and S. aureus in vitro when the antibacterial model drug amoxicillin was encapsulated in the hydrogels. A lap-shear test was also carried out with these hydrogels. The hydrogels exhibited good mucosal adhesion, indicating their potential use in mucosa-localized drug delivery systems. All these results suggest that these injectable pH-responsive adhesive hydrogels are ideal candidates for development of colon cancer drug delivery carriers or mucoadhesive drug delivery systems.