Quercetin-loaded gelatin/agarose/Fe2O3 hybrid nanocarriers in a microemulsion matrix: synthesis, characterization, and cancer therapeutic potential

Innovative therapeutic approaches to maximize efficacy and reduce systemic toxicity are needed to combat the growing global burden of cancer. The research provides pH-sensitive hybrid nanocarriers (G-Aga-Fe₂O₃) based on gelatin, agarose, and iron oxide for controlled quercetin (QC) delivery, a flavonoid with anticancer activity. Hydrothermally synthesized nanocarriers were incorporated in a sesame oil-based microemulsion structure for controlled drug release. XRD, FTIR, FESEM, and DLS indicated successful synthesis of 152 nm average hydrodynamic diameter spherical nanocarriers, a zeta potential of −40 mV with excellent colloidal stability, and good chemical interfaces between QC and the matrix. Hydrogen bonding and amorphous structural integration of Fe₂O₃ ensure the integrity of nanocarriers, as suggested by FTIR and XRD data. The platform outperformed multiple platforms with respect to encapsulation efficiency (85.25 %) and drug loading (43.75 %). In accordance with the Hixson-Crowell model, pH-sensitive release kinetics obtained 95 % QC release at tumor-mimicking acidic pH (pH 5.4) vs. 60 % under physiological pH (pH 7.4), indicating tumor-targeting. In vitro cytotoxicity tests on MCF-7 cells showed 46 % cell mortality, which was better than free QC, while the common L929 cells still had 96 % viability and proved biocompatibility. G-Aga-Fe₂O₃ proved to be an innate stable and pH-sensitive platform for advancing the therapeutic effect of quercetin in cancer treatment. Gelatin/Agarose/Fe 2 O 3 nanocarrier hybrid system loaded with quercetin in a microemulsion matrix • Hybrid nanocarriers demonstrated high stability and remarkable encapsulation and drug loading efficiencies. • The developed pH-sensitive nanocarrier system not only enhanced drug entrapment but also enabled controlled, sustained release. • The developed quercetin-loaded nanocarrier system achieved a 46 % cancer cell mortality rate in MTT assays.