Gelatin-Oxidized\nAlginate and Chitosan-Coated Zein\nNanoparticle Hydrogel Composite to Enhance Breast Cancer Cytotoxicity\nin Dual-Drug Delivery

This study explores the combined delivery of doxorubicin\nand quercetin\nusing a gelatin-oxidized alginate-based hydrogel as a promising strategy\nfor localized breast cancer therapy. Our approach involves the incorporation\nof doxorubicin within the hydrogel matrix and loading quercetin into\nchitosan-coated zein nanoparticles. The hydrogel exhibited self-healing\nproperties attributed to Schiff base cross-linking and demonstrated\ninjectability. Characterization of its microstructural, mechanical,\nand textural properties revealed a porous and flexible structure,\ndemonstrating its suitability for drug release applications. Both\ndrugs exhibited distinct in vitro release profiles at pH 6.8 (typical\nof tumor tissue), with doxorubicin at 81.2% and quercetin at 9.7%.\nAfter 72 h of release, the cytotoxicity against MCF-7 breast cancer\ncells was assessed. The hydrogel formulation containing doxorubicin\nincreased the cytotoxic action by 4.66-fold, whereas the hydrogel\ncomposite, containing both doxorubicin and quercetin-loaded nanoparticles,\nenhanced it by 20.7-fold compared with doxorubicin alone. Thus, the\nfindings of our study highlight the enhancing effect of the dual release\nsystem, thereby expanding the utility of gelatin-oxidized alginate-based\nhydrogels as advanced drug delivery systems, as exemplified by the\ncombined delivery of doxorubicin and quercetin.