Abstract
Cervical cancer remains a significant health challenge in developing countries are high due to low HPV vaccination rates, delayed diagnosis, and restricted healthcare access. Metal nanomaterials, such as copper oxide (CuO) nanoparticles (NPs), have shown significant promise in cancer therapy due to their ability to induce apoptosis. 5-Fluorouracil (5-Fu) enhances the cytotoxic effect against cervical cancer, working synergistically with CuO NPs to maximize the therapeutic impact while potentially reducing the 5-Fu's systemic side effects. This study explores the synergistic therapeutic potential of green-synthesized CuO NPs combined with 5-Fu in a gel formulation for targeted anticancer activity against HeLa cervical cancer cells. CuO NPs were synthesized using Trichosanthes dioica dried seeds extract and incorporated into a pectin-xanthan gum-based gel. The green-synthesized CuO NPs exhibited a zeta potential of -23.7 mV, a particle size of approximately 26 nm, and spherical morphology. Characterization studies, including FTIR, viscosity, spreadability, pH, and stability assessments, confirmed the gel's suitability for vaginal delivery. In-vitro drug release showed xanthan gum extended the release up to 8 h. The MTT assay revealed PXFCu6 gel's IC(50) at 11.82 ± 0.22 μg/mL, significantly more cytotoxic to HeLa cells, being 3.62 times potent than CuO NPs (IC(50): 42.8 ± 0.24 μg/mL) and 1.63 times potent than 5-Fu alone (IC(50): 19.3 ± 0.49 μg/mL). The antibacterial assay showed no inhibition for the plain gel, but T. dioica-mediated CuO NPs exhibited inhibition of 22.35 ± 4.9 mm. PXFCu6 gel had the more potent inhibition at 52.05 ± 1.37 mm against Escherichia coli growth. The PXFCu6 gel showed better stability at 4 °C, maintaining viscosity, pH, and drug release, unlike 25 °C where a mild degradation occurred. This research highlights the potential of the CuO NPs-5-Fu gel as a novel, effective therapeutic strategy for cervical cancer treatment.