Pterostilbene lipid nanocapsules as a promising system for treatment of hepatocellular carcinoma: Formulation, characterization, and cellular/in vivo appraisal

Published: 2024
Journal of Drug Delivery Science and Technology, Volume 92
ISBN: 1773-2247


Pterostilbene has shown very promising traits as a nutraceutical compound, especially in the field of cancer treatment. However, its poor aqueous solubility hinders its clinical applicability. The purpose of this work was to enhance the antitumoral activity of pterostilbene in hepatic cancer via encapsulation in lipid nanocapsules. Pterostilbene nanocapsules were prepared using the phase inversion technique. One gram of Kolliphor® HS 15 dissolved in 3 g of distilled water was added to 1 g of isopropyl myristate containing 150 mg Epikuron 200 and 100 mg pterostilbene under magnetic stirring, while applying three temperature cycles alternating between 55 and 85 °C for phase inversion to occur. Shock cooling of the dispersion was induced by introduction of 5 g of distilled water, followed by stirring for 30 min. The nanocapsules were characterized for the particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphology, antitumoral activity in HepG2 liver cancer cell line in terms of viability, assessment of cell death mode and cycle arrest, cellular localization assessment, and quantification of cellular uptake. The in vivo antitumoral activity of lipid nanocapsules was further verified using a chemically-induced hepatic cancer model using diethylnitrosamine and carbon tetrachloride. Several biochemical markers were quantified, followed by histopathological examination. Results displayed the potential of pterostilbene in treatment of liver cancer, with the enhancement of its therapeutic efficacy by encapsulation in lipid nanocapsules, as evidenced by further decreased levels of ALT, AST, AFP, Bcl2, VEGF, NF-kB, ERK, AKT, with concomitant increase in caspase3 level, while showing comparable histological features to the normal control group. Pterostilbene nanocapsules were proven promising in the treatment of hepatocellular carcinoma, deserving further preclinical and clinical evaluation.
Keywords: Pterostilbene; Lipid nanocapsules; Liver cancer; Nutraceuticals