Gold Nanoparticle-Based Hydrogel: Application in Anticancer Drug Delivery and Wound Healing In Vitro

<b>Background/Objectives</b>: Due to the challenges faced by anticancer therapeutics, such as poor selectivity and metabolic degradation, novel delivery systems are needed to mitigate the adverse effects of chemotherapy. The management of chronic wounds is often overlooked and affects patients mentally and physically. The application of hydrogels can reduce deficiencies in drug delivery and wound healing due to their similarity to the extracellular matrix and stimuli-responsive properties. <b>Methods</b>: A chitosan (CS) hydrogel, cross-linked to gold nanoparticles (AuNPs), followed by the encapsulation of 5-fluorouracil (5-FU), was formulated. The physicochemical properties, drug release profiles, cytotoxicity, and wound healing in vitro were analyzed. <b>Results</b>: Fourier transform infrared spectroscopy and a UV-visible peak at 530 nm confirmed their successful synthesis. Transmission electron microscopy revealed spherical NPs of 89.31 nm, while scanning electron microscopy confirmed the porous network surface of the hydrogels. The thermogravimetric analysis demonstrated enhanced stability for the CS-Au hydrogel, while a non-Newtonian shear-thinning property was evident from rheology. Drug release showed a sustained, pH-dependent release with specificity for the acidic cancer microenvironment. The cytotoxicity assay demonstrated a specificity of the CS-Au-5-FU hydrogel for the cancer cells (HeLa and MCF-7) and diminished cytotoxicity in the non-cancer cells (HEK293). The scratch assay illustrated a complete closure of the wounds in HEK293 cells at low concentrations (15.63 and 31.25 µg/mL). <b>Conclusions</b>: The positive findings from this study confirm the potential of these CS-Au hydrogels to function as smart in vitro delivery systems and scaffolds for wound healing, warranting additional optimizations and in vivo studies.