Formulation of hispidulin-loaded sodium carboxymethyl cellulose nanoparticles: characterisation, biological activities and molecular insights

Background Hispidulin is a bioactive flavonoid with promising antioxidant and anticancer properties; however, its poor aqueous solubility and stability limit its usage in therapeutic application. This study aimed to develop a suitable nanocarrier system to enhance its bioavailability and biological efficacy. Methods Hispidulin-loaded sodium carboxymethyl cellulose nanoparticles (HIS-CMC NPs) were synthesised via ionic gelation. Physicochemical characterisation was performed using UV–Vis, FTIR, XRD, DLS and TGA, along with microscopic analysis. Encapsulation efficiency and drug loading were determined. In vitro drug release and kinetic modelling were conducted. Biological activities, including antioxidant, anti-inflammatory, metal chelating, lipid peroxidation inhibition, hemocompatibility, thrombolytic activity, and cytotoxicity (MCF-7 and 3T3-L1 cells) were evaluated. Apoptosis and mitochondrial membrane potential were assessed using Hoechst and TMRE staining. Molecular docking with VEGFR and ADMET analysis were also performed. Results The HIS-CMC NPs showed a hydrodynamic size of 243.3 nm and a zeta potential of −39.1 mV, indicating good stability. High encapsulation efficiency (94.84% ± 1.2%) and drug loading (35.13% ± 1.5%) were achieved. Sustained drug release (87.5% ± 1.3%, pH 5.4) followed Korsmeyer–Peppas kinetics. The nanoparticles exhibited enhanced antioxidant, anti-inflammatory and metal chelating activities compared to free hispidulin. They demonstrated good hemocompatibility (3.60%) and thrombolytic activity (69.62%). Selective cytotoxicity towards MCF-7 cells (IC 50 = 35.33 μg/mL) with minimal toxicity to 3T3-L1 cells was observed. Biopolymeric NPs showed apoptosis and mitochondrial depolarisation in MCF-7 cells. Docking studies revealed strong binding affinity to VEGFR (−9.7 kcal/mol), supported by favourable ADMET properties. Conclusion HIS-CMC NPs exhibit improved stability, sustained release and enhanced biological activity, indicating their potential as an effective nanocarrier for anticancer applications.