Abstract
Kaempferol, a phytomolecule currently in Phase I clinical trials, is also being explored for its nutraceutical potential. However, its clinical utility is limited due to poor bioavailability. Previous studies suggest that intravenous administration of PEGylated liposomes can markedly improve the pharmacokinetic profile and systemic availability of phytochemicals, while enabling controlled release through the enhanced permeability and retention (EPR) effect. In the present study, we prepared and validated polyethylene glycol (PEG) modified Kaempferol liposome which possess a particle size, polydispersity index (PDI) and zeta potential of 136.60 ± 0.37 nm, 0.1540 ± 0.020 and -37.0 ± 8.19 mV respectively. PEG-LP-KP exhibited an entrapment efficiency of ~ 92% and shows a sustained Kaempferol release upon 24 h at pH 5.5. Our study indicates that intravenous administration of PEG-LP-KP significantly improves the pharmacokinetic parameters such as AUC(0-24), Cmax and Vd compared with pure Kaempferol at three different doses (10 mg/kg, 20 mg/kg & 30 mg/kg). The biodistribution study indicated that Kaempferol encapsulated into the liposome shows a high accumulation in the liver, followed by spleen, lungs, heart, and kidneys of healthy SD rats. The biodistribution pattern of PEG-LP-KP was significantly improved compared with that of pure Kaempferol. PEG-LP-KP exhibited significant cytotoxicity in HepG2 cells with an IC50 of 153.57 μM as assessed by the MTT assay. PEG-LP-KP demonstrated a favorable safety profile, as evidenced by both acute and sub-acute toxicity assessments. We also found a significant tumor reduction in PEG-LP-KP treated animal groups compared to vehicle control as assessed by Orthotopic syngeneic N1S1 rat model.
Acknowledgements
We express our gratitude for the inspirational guidance of Sri Mata Amritanandamayi Devi at Amrita Vishwa Vidyapeetham. We would also like to thank Dr. Shanti Kumar V. Nair, Associate Provost of Academics at Amrita Vishwa Vidyapeetham, for the facilities provided. We thank Dr. Deepthy Menon, Professor, Amrita School of Nanosciences and Molecular Medicine, Kochi, for providing the ultrasound scanning facility for conducting animal study. We thank Dr. Vyshak Mohan M, Veterinarian, iVET Lab, Kochi, for his valuable support in conducting the histopathological evaluation of organs and for his expert interpretation of the results. We thank Ms. Abna Ansar, Department of Biostatics, Amrita School of Pharmacy, Kochi, for her valuable assistance with the statistical interpretation of the research findings. We extend our thanks to Ms. Devi S., Faculty in Learning and Development (Verbal and Communication Skills) in Corporate and Industry Relations at Amrita Vishwa Vidyapeetham, for her assistance with the language editing of this research article. We thank Ms. Gaythri Sudevan, Ms. Kavya A. Arun, and Mr. Abir Chakraborty for their technical support in completing the study.
Funding
Open access funding provided by Amrita Vishwa Vidyapeetham. We acknowledge the support from the Amrita Vishwa Vidyapeetham SEED grant [Project ID: K-PHAR-22-662] to LRN & Amrita Vishwa Vidyapeetham Ph.D fellowship to ARK. We also acknowledge the Department of Science and Technology, India, for providing the DST INSPIRE PhD fellowship (1F230219) to AJK.
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Kumar, A.R., Dharshini, M.D., Devan, A.R. et al. PEGylated liposomes enhance the pharmacokinetics, biodistribution, anticancer efficacy, and safety of Kaempferol, a phytomolecule enrolled in clinical trials. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51900-5
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DOI: https://doi.org/10.1038/s41598-026-51900-5
