Synthesis and characterization of self-crosslinked carboxymethyl chitosan-based hydrogel and its composites with gelatin and PEG-GO for drug delivery applications

Hydrogels are widely employed in drug delivery, gene delivery, tissue engineering, and wound healing applications. However, many organic crosslinkers used in hydrogel fabrication exhibit poor water solubility, low biodegradation rates, and toxicity, limiting their biomedical utility. In this study, we developed a simple, cost-effective, and rapid method for synthesizing self-crosslinked carboxymethyl chitosan-based hydrogel (CMCH HG) using N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-Hydroxysuccinimide (NHS) chemistry instead of toxic organic crosslinkers. To enhance physicochemical properties, we prepared composites of self-crosslinked hydrogel with gelatin (CMCH/GL HG) and 6-arm polyethylene glycol amine-functionalized graphene oxide (CMCH/GL/PEG-GO HG). The fabrication and physicochemical characteristics of the self-crosslinked hydrogel and its composites were verified through analytical and spectroscopic techniques. The in-vitro drug release study using berberine chloride demonstrated that CMCH/GL/PEG-GO HG released only 30 % of the drug in the first 12 h and a total of 39 % after 96 h. Due to controlled drug release, excellent antioxidant activities, anticancer properties, biodegradability, and minimal toxicity, the composite of self-crosslinked carboxymethyl chitosan hydrogel with gelatin and graphene oxide represents a promising candidate as a drug carrier at tumor sites to minimize off-target effects of chemotherapy.