Development of a pH-responsive starch-based nanocarrier polyacrylic acid containing SiO₂ for controlled quercetin release in cancer therapy

Cancer is still a major worldwide health concern, and traditional treatment methods can have serious side effects. In order to improve the therapeutic use of quercetin (QC) in the treatment of cancer, this work presents a newly developed pH-responsive nanocomposite. The water-in-oil-in-water (W/O/W) double emulsion approach was used to create the nanocarrier, which is an effective QC delivery system made up of silica nanoparticles (SiO₂), polyacrylic acid (PAA), and starch (S). With entrapment and loading efficiencies of 79.50% and 46%, respectively, the addition of SiO₂ nanoparticles greatly improves the S/PAA hydrogel matrix’s entrapment and drug-loading capabilities. the dynamic light scattering (DLS) studies, zeta potential, and field emission scanning electron microscopy (FE-SEM) showed the average particle size to be 171.25 nm and zeta potential to be -50.12 mV, demonstrating a stable well-defined nanoscale structure. The pH-sensitive character of the prepared nanocarrier is further highlighted by in vitro drug release studies that show QC is released in a sustained and controlled way in acidic media compared to physiological pH. The Higuchi model has the best fit at pH 7.4, indicating that drug diffusion is mainly controlled by solubility constraints in the polymer matrix. The Korsmeyer-Peppas model, on the other hand, has the most accurate representation at pH 5.4, indicating an anomalous transport mechanism. These mathematical models further clarify the release kinetics. Furthermore, cytotoxicity tests employing the MTT assay verify the QC-loaded nanocomposite’s strong inhibitory effects on HCT-116 colon cancer cells while proving its biocompatibility with L929 fibroblast cells. Together, our results demonstrate the S/PAA/SiO₂@QC nanocomposite’s potential as an effective and focused therapeutic platform for the treatment of cancer, providing a viable substitute for traditional drug delivery methods.