Formulation of hispidulin-loaded sodium carboxymethyl cellulose nanoparticles: characterisation, biological...

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.

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.

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 (IC₅₀ = 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.

HIS-CMC NPs exhibit improved stability, sustained release and enhanced biological activity, indicating their potential as an effective nanocarrier for anticancer applications.