Gelatin-Oxidized Alginate and Chitosan-Coated Zein Nanoparticle Hydrogel Composite to Enhance Breast Cancer Cytotoxicity in Dual-Drug Delivery

Abstract

This study explores the combined delivery of doxorubicin and quercetin using a gelatin-oxidized alginate-based hydrogel as a promising strategy for localized breast cancer therapy. Our approach involves the incorporation of doxorubicin within the hydrogel matrix and loading quercetin into chitosan-coated zein nanoparticles. The hydrogel exhibited self-healing properties attributed to Schiff base cross-linking and demonstrated injectability. Characterization of its microstructural, mechanical, and textural properties revealed a porous and flexible structure, demonstrating its suitability for drug release applications. Both drugs exhibited distinct in vitro release profiles at pH 6.8 (typical of tumor tissue), with doxorubicin at 81.2% and quercetin at 9.7%. After 72 h of release, the cytotoxicity against MCF-7 breast cancer cells was assessed. The hydrogel formulation containing doxorubicin increased the cytotoxic action by 4.66-fold, whereas the hydrogel composite, containing both doxorubicin and quercetin-loaded nanoparticles, enhanced it by 20.7-fold compared with doxorubicin alone. Thus, the findings of our study highlight the enhancing effect of the dual release system, thereby expanding the utility of gelatin-oxidized alginate-based hydrogels as advanced drug delivery systems, as exemplified by the combined delivery of doxorubicin and quercetin.