Gelatin-Oxidized Alginate and Chitosan-Coated Zein Nanoparticle Hydrogel Composite to Enhance Breast Cancer Cytotoxicity in Dual-Drug Delivery
Sanierlly da Paz do Nascimento, Ramon Ramos Marques de Souza, Marianna Vieira Sobral, Francisco Humberto Xavier Júnior, Marcus Vinícius Santos da Silva, Marcelo Vianna, Fausthon Fred da Silva, Michael J. Serpe, A. L. Souza
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.