Reactive oxygen species-responsive hydrophobic crosslinked chitosan films based on triple-function crosslinkers

Chitosan is widely used in reactive oxygen species (ROS)-responsive films but remains great challenges owing to its weak mechanical strength and strong hydrophilicity. Herein, we synthesized novel hydrophobic crosslinked CS films with ROS-responsive properties and excellent physicochemical properties. A novel crosslinker, 2-((10-carboxydecyl)thio)succinic acid, with long-chain alkanes, three carboxyl groups, and sulfhydryl groups was synthesized and then used to produce thioether-containing crosslinked CS membranes. The results suggested that crosslinking could significantly increase the tensile strength of the film from 15.67 MPa to 24.32 MPa. The compact structure of crosslinked chitosan film improved the hydrophobicity and degradability, reduced the thermal stability and swelling rates, exhibited excellent non- cytotoxicity. The in vitro release studies revealed that crosslinked chitosan films could displayed the highest flux about 1.40 mg/ (cm² h) and significant NR fluorescence change over 80 %. Collectively, our results demonstrate the applicability of these films as ROS-responsive drug delivery systems.