Engineered mesoporous silica nanoparticles for the co-delivery of quercetin and resveratrol: structural characterization and assessment of antioxidant and anti-inflammatory potential

Abstract

The global burden of noncommunicable diseases (NCDs) is closely associated with persistent oxidative stress and chronic inflammation. Natural polyphenols such as quercetin and resveratrol possess potent antioxidant and anti-inflammatory activities; however, their therapeutic potential is severely hindered by low aqueous solubility, poor chemical stability, and rapid metabolic degradation. Nanotechnology-based delivery systems offer a promising approach to enhance the bioavailability and functional performance of these bioactive compounds. Accordingly, this work aimed to co-encapsulate quercetin and resveratrol into mesoporous silica nanoparticles (MSNs), thoroughly characterize the resulting nanocarrier system, and assess its biological properties in vitro. MSNs were synthesized through a modified Stöber method, yielding uniform, spherical, amorphous nanoparticles with an average hydrodynamic diameter of ~126 nm, a high specific surface area (200.3 m²/g), a pore volume of 0.445 cm³/g, and a mean pore diameter of 5.4 nm. Co-loading was achieved using a solvent evaporation method, resulting in high encapsulation efficiencies (79.9% for quercetin and 71.4% for resveratrol). Physicochemical characterization (FTIR, XRD, TGA, DLS, Zeta Potential) confirmed successful drug incorporation, partial amorphization of the polyphenols, enhanced thermal stability, and a sustained release profile extending to 75 hours. The QUE-RES-SiO₂ formulation demonstrated significantly enhanced antioxidant capacity in DPPH, CUPRAC, and ABTS assays, surpassing free resveratrol. Strong anti-inflammatory capacity was also observed in a heat-induced protein denaturation model, with up to 75% inhibition, comparable to free quercetin and the reference drug diclofenac. In ovarian adenocarcinoma SKOV-3 cells, the formulation exhibited efficient nanoparticle uptake; however, it did not induce cytotoxicity or reactive oxygen species (ROS) production within 24 hours, likely due to slow-release kinetics, intrinsic chemoresistance of the cell line, and low concentrations tested over a limited time. Overall, these results demonstrate that MSNs constitute an effective platform for the co-delivery of quercetin and resveratrol, enhancing their stability and antioxidant and anti-inflammatory potential while overcoming key physicochemical limitations. Although anticancer effects were not observed under the tested conditions, this study establishes a robust foundation for future optimization of release kinetics, dosing strategies, and targeting mechanisms to exploit the therapeutic potential of polyphenols in oxidative stress- and inflammation-driven chronic diseases.