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Cholesterol-conjugate as a new strategy to improve cytotoxic effect of 5-fluorouracil on liver cancer: impact of liposomal composition

Author(s):

Saleh A. Alanazi*, Gamaleldin I. Harisa, Mohamed M. Badran, Nazrul Haq , Awwad A. Radwan , Ashok Kumar , Faiyaz Shakeel and Fars K. Alanazi*  

Abstract:


Purpose: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is a clinically recognized to treat HCC. However, the success of this therapy is highly limited due to rapid clearance and non- selective distribution. Cholesterol-conjugate (5-FUC) loaded liposomes proposed to facilitate the transport of 5-FUC into tumor cells via low-density lipoprotein receptor (LDL receptor) that overexpressed in HCC. Thus, the aim of this study was to use 5-FUC loaded liposome as a promising strategy to combat HCC and improve the response of HCC to chemotherapy.

Methods: 5-FUC and 5-FU loaded liposomes were optimized based on cholesterol (CHO) ratio and type of phospholipid to achieve a potential effect on HCC. Liposomes were prepared by the thin-film hydration method, and evaluated in terms of particle size, polydispersity, zeta potential, entrapment efficiency (EE), morphology, drug release and cytotoxicity.

Results: The obtained liposomes had a suitable nano-range particle size with negative zeta potential, and acceptable EE%. In vitro drug release of 5-FUC loaded liposomes showed a lower cumulative release over 24 h compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect compared to the free drug and 5-FU loaded liposomes against HepG2 cell lines after 48 h via MTT assay.

Conclusion: These results concluded that 5-FUC loaded liposomes could be used as an alternative tactic to increase the therapeutic index of 5-FU and pave the way for potential clinical applications.

Keywords:

5-fluorouracil, Phospholipids, Liposomes, Drug delivery , Liver cancer , Cytotoxicity

Affiliation:

Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh



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