Ternary complex of Kaempferol-Hydroxypropyl-β-Cyclodextrin-Liposomes against hepatocellular carcinoma: Preparation,...

Kaempferol (KP), a GRAS-certified phytomolecule enrolled in Phase I trials, is reported with various biological effects including anticancer activity. However, its poor pharmacokinetic profile limits the translational utility. Studies indicate that liposomes incorporating cyclodextrin inclusion complexes improves the bioavailability of hydrophobic drugs. The present study focuses on preparing and validating a novel ternary complex of Kaempferol-Hydroxypropyl-β-Cyclodextrin-Liposomes (KP-HP-β-CD-Liposomes) that shows a particle size of 131.70 ± 0.10 nm, a zeta potential of -26.59 ± 0.42 mV, and a drug entrapment efficiency of 90.14 ± 0.25 %. The KP-HP-β-CD-Liposomes demonstrate stability under refrigerated conditions (2-8 °C) over a three-month period. Also, it doesn't exhibit any cytotoxicity in normal fibroblast cells even up to 48 mg/ml while it produces a dose dependent cytotoxicity in HepG2 cells. It shows a better cellular uptake in HepG2 cells in comparison with pure Kaempferol as evidenced by HPLC analysis. KP-HP-β-CD-Liposomes induce apoptosis in HepG2 cells as assessed by Acridine orange ethidium bromide staining. Pharmacokinetic studies on Sprague Dawley rats indicate a significant improvement in Cmax and AUC_(0-∞) of Kaempferol. The tissue distribution studies show that KP-HP-β-CD-Liposomes are highly accumulated in liver. The KP-HP-β- CD-Liposomes inhibits the development of hepatic tumors in Syngeneic N1S1 animal models.