Nanobiofunctionalized chitosan nanocomposite hydrogel as a highly biocompatible cancer drug carrier

A bio-inspired drug carrier was developed by dual functionalization of chitosan using L-glutamic acid (GA) and phyto-synthesized zinc oxide nanoparticles (ZNPs). A highly porous, three-dimensional network of nanocomposite hydrogel (GA-CHGZ) was obtained upon cross-linking chitosan using biomass-derived dialdehyde cellulose. The hydrogel was optimally loaded with naringenin (NRG) and further characterized using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and swelling studies. An enhanced NRG loading efficiency of 85.23% was obtained using functionalized hydrogel compared to 52.54% using non-functionalized hydrogel. Delivery studies displayed a maximum release of 69.63% for 1.0 mg/ml of initial NRG concentration at pH 5, which is a highly preferred condition for cancer therapeutics. While ZNPs’ embedment was instrumental in improving the NRG loading and delivery rates, the GA conjugation increased the stability of NRG in the GA-CHGZ, aiding sustained NRG release, which followed a non-Fickian diffusion mechanism with polymer swelling. Antimicrobial potential was explored against Staphylococcus aureus and Trichophyton rubrum strains. The biocompatibility assay using L929 normal cells showed enhanced cell proliferation characteristics for the materials, revealing significant cell viability. The anticancer activity of NRG tested against A431 human skin carcinoma cells increased up to nine-fold with a reduced IC₅₀ value when a functionalized hydrogel was used instead of pure NRG without the nanocomposite carrier. Thus, the bio-functionalized drug–carrier system has a promising application for wound healing and topical skin cancer therapies.