Synthesis of Dialdehyde Chitosan‐Based Schiff Base Polymeric Complexes for the Controlled Delivery of 5‐Fluorouracil (5‐FU) in Skin Cancer

Abstract Skin cancer has emerged as the fifth most reported cancer in the world, causing a burden on global health. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as therapeutic agents and drug carriers for remarkable skin cancer treatment. Therefore, first, we synthesized dialdehyde chitosan (DCH) as a cross‐linking agent using sodium meta periodate by dark synthesis and developed a three‐dimensional hydrogel using chitosan (CH), incorporating 5‐fluorouracil (5‐FU) as an anticancer drug and DCH as a cross‐linking agent. The hydrogel formation follows the principle of the Schiff‐based polymeric complex. The 5‐FU‐loaded hydrogels released faster and reached a higher cumulative release rate of 94.58% in 5.5 pH phosphate buffer saline (PBS), 97.89% in 7.4 pH PBS, and 98.34% in 5 pH acetate buffers within 12 h. The compatibility of drug and excipients was confirmed by Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction calorimetry (X‐RD), and differential scanning calorimetry (DSC) to evaluate the thermal properties of the drug, polymer, and prepared hydrogel formulation and scanning electron microscopy (SEM) to evaluate the microstructure of the prepared hydrogel. To understand their efficacy, the optimized formulation was evaluated for in vitro cytotoxicity screening using the B16F10 skin cancer cell line. The developed topical hydrogel exhibited significant anticancer efficacy against skin cancer cells in in vitro cell line studies.