1. Ternary complex of Kaempferol-Hydroxypropyl-β-Cyclodextrin-Liposomes against hepatocellular carcinoma: Preparation, validation, pharmacokinetics and efficacy studies.
- Author
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Sah SK, Ajay SA, Donadkar AD, Kamath AJ, Devan AR, Soman R, Kumar AR, Unni AR, Sithara MS, Sudheesh MS, and Nath LR
- Subjects
- Animals, Humans, Hep G2 Cells, Male, Apoptosis drug effects, Rats, Cell Survival drug effects, Particle Size, Drug Stability, Tissue Distribution, Kaempferols pharmacokinetics, Kaempferols administration & dosage, Kaempferols chemistry, 2-Hydroxypropyl-beta-cyclodextrin chemistry, Liposomes, Liver Neoplasms drug therapy, Carcinoma, Hepatocellular drug therapy, Rats, Sprague-Dawley
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)- Published
- 2025
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