Reduction-Responsive Chitosan-Based Injectable Hydrogels for Enhanced Anticancer Therapy

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, which leads to the death of cancer cells while simultaneously minimizing the negative effects of chemotherapy on other tissues, thereby improving the patient's quality of life. To address this need, we developed reduction-responsive chitosan-based injectable hydrogels via the inverse electron demand Diels-Alder reaction between tetrazine groups of disulfide-based cross-linkers and norbornene groups of chitosan derivatives, which were applied to the controlled delivery of doxorubicin (DOX). The swelling ratio, gelation time (90-500 s), mechanical strength (G'similar to 350-850 Pa), network morphology, and drug-loading efficiency (>= 92%) of developed hydrogels were investigated. The in vitro release studies of the DOX-loaded hydrogels were performed at pH 7.4 and 5.0 with and without DTT (10 mM). The biocompatibility of pure hydrogel and the in vitro anticancer activity of DOX-loaded hydrogels were demonstrated via MTT assay on HEK-293 and HT-29 cancer cell lines, respectively.

Automated summary

Selective delivery of anticancer drug molecules to the tumor site enhances local drug dosages, improving the patient's quality of life by minimizing the negative effects of chemotherapy. In this study, we developed a reduction-responsive chitosan-based injectable hydrogel for controlled delivery of doxorubicin (DOX). The hydrogel exhibited proper swelling ratio, gelation time, mechanical strength, network morphology, and high drug-loading efficiency (>= 92%). In vitro release studies showed pH-dependent drug release, and the hydrogel demonstrated biocompatibility and anticancer activity against HEK-293 and HT-29 cancer cell lines.