Chitosan‐based self‐healing hydrogel mediated by poly(acrylic‐methacrylic acid) exhibiting high biocompatibility and anti‐tumor activity

Abstract Multi‐responsive, self‐healing hydrogels were developed utilizing positively charged polysaccharides, chitosan, and water‐soluble chitosan. This fabrication employed free‐radical synthesized polyacrylic acid and polymethacrylic acid along with the cross‐linker FeCl 3 , resulting in the generation of polyelectrolyte metal complexes, which enhances the properties of the chitosan‐based hydrogels, particularly their mechanical strength, self‐healing ability, thermal stability, swelling behavior, porous structure, cell viability, and even anticancer activity. Characterization and stability assessment of the hydrogels were performed using FT‐IR, nuclear magnetic resonance, gel permeation chromatography, scanning electron microscopy, rheometer, x‐ray diffraction, thermogravimetric analysis, DSC, and UV spectroscopy. FT‐IR measurements indicated that the facile complexation of the cross‐linker's metal ions (Fe 3+ ) with the carboxylate (COO − ), amino (NH), and hydroxyl (OH) groups of the polymers and chitosan chains facilitated rapid gelation. Furthermore, the sustained release of the drug levofloxacin (up to 80%) was observed to increase with increasing pH due to the hydrogels' anionic nature. Biocompatibility and cytotoxicity tests were conducted using the MTT assay on splenocytes and Dalton Lymphoma cancer cell lines. These tests demonstrated the promising potential of these hydrogels for drug delivery applications.