Novel carbohydrate-based nanomedicine: A pH-responsive cyclodextrin/Zein/TiO₂ nanoemulsion for sustained release and enhanced anti-cancer effects of quercetin

Nanocarriers derived from carbohydrate polymers offer a promising approach to overcoming the limitations of conventional cancer therapies, particularly by enhancing tumor targeting and enabling sustained drug release. A novel nanoemulsion based on Cyclodextrin, Zein, and TiO₂ nanoparticles was developed and loaded with Quercetin as the therapeutic agent to address these challenges. The interactions among the nanoemulsion components were characterized using FTIR spectroscopy, while XRD provided insights into their crystallinity. The nanoemulsion exhibited a spherical morphology with a size range between 80–120 nm, confirmed by SEM and DLS. Zeta potential results indicated higher stability in blood circulation with around -50 mV surface charge. High loading and encapsulation efficiency showed the impact of TiO₂ in nanoemulsion by improving LE % and EE % to 47.5 % and 87.75 %, respectively. The in vitro release results in different pH circumstances (7.4 and 5.4) indicated controlled, pH-sensitive release behavior over 96 h. The experimental data fitted into various release kinetic models and determined the best release mechanisms. The MTT assay demonstrated the nanocarrier's selective toxicity on A549 and L929 cell lines, as cancerous and normal cells, respectively. The results indicate the biocompatibility of Quercetin-loaded nanoemulsion and its positive effect on higher A549 cellular inhibition by a controlled higher release rate of Quercetin in the target site. These results suggest that the developed nanocarrier holds promise for addressing the challenges associated with conventional lung cancer treatments through controlled and targeted drug delivery.