Formulation of Surface-Modified Quercetin-Loaded Chitosan-Hyaluronic Acid Nanoparticles for Targeted Hepatic Cancer Therapy

Abstract Hepatic cancer remains one of the most difficult conditions to cure, particularly when it comes to detecting and eliminating malignant metastases. In this study, the potent anticancer agent quercetin (QU) was effectively encapsulated in the biocompatible polymer chitosan (CS) to enhance its poor water solubility. The resulting QU-loaded nanoparticles (QU-NPs) were formulated using CS, a polysaccharide derived from the deacetylation of chitin. Hyaluronic acid (HA) was employed as a capping and targeting agent, and lactoferrin was added to improve drug bioavailability. The final formulation, lactoferrin-coated, HA-capped CS NPs loaded with quercetin (QCHL-NPs), exhibited strong adherence to liver cancer cell surfaces. The synthesized NPs were characterized using zeta potential analysis, particle size analysis, HR-TEM, and UV-Vis spectroscopy. The in vivo safety of QCHL-NPs was confirmed through toxicity assays on HepG2 cells. In vitro cytotoxicity data showed that QCHL-NPs required significantly lower concentrations than free QU to achieve over 60% inhibition (IC₅₀). Treatment with QCHL-NP also significantly reduced antioxidant levels, while caspase-3 analysis revealed apoptosis at the molecular level. Notably, this study successfully synthesized QCHL-NPs with enhanced QU loading. In HepG2 cells, the formulation demonstrated improved targeted delivery and greater antitumor efficacy compared to free QU.