Design, Optimization and Physicochemical Characterization of Pectin-Based Nanoparticles for In Vitro Anticancer Evaluation Against HCT116 Colon Cancer Cells

Introduction: Cancer is a major global health problem characterized by uncontrolled cell proliferation, dysregulated cell cycle progression, and the ability of malignant cells to invade and metastasize to distant organs. Natural flavonoids such as rutin and hesperidin have demonstrated promising anticancer properties; however, their therapeutic application is limited due to poor aqueous solubility and low bioavailability. Method: Therefore, the present study aimed to enhance the solubility and colon-targeting efficiency of rutin and hesperidin by formulating them into pectin-based nanoparticles. Pectin nanoparticles encapsulating rutin and hesperidin were prepared using the Probe Sonicator/High-Pressure Homogenizer (HPH) technique. The developed nanoparticles were characterized using X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) analysis. results: The optimized nanoparticles exhibited nanoscale size distribution with uniform morphology and high encapsulation efficiency. XRD and DSC analyses confirmed reduced crystallinity of the encapsulated flavonoids, indicating improved solubility. In vitro cytotoxicity studies demonstrated significantly enhanced antiproliferative activity of rutin- and hesperidin-loaded pectin nanoparticles compared to free compounds. The enhanced activity may be attributed to improved cellular uptake and sustained drug release. Mechanistically, flavonoid-loaded nanoparticles were associated with modulation of oxidative stress, induction of apoptosis, and cell cycle arrest in HCT116 cells. Results and Discussion: Characterization studies confirmed nanoscale particle formation with suitable morphology and improved stability. Furthermore, the nanoformulation exhibited enhanced cytotoxic potential against colon cancer cells. Conclusion: Pectin-based nanoparticles significantly improved the solubility and anticancer potential of rutin and hesperidin, indicating their promising role as a colon-targeted drug delivery system for colorectal cancer therapy.