Cholesterol-Conjugate as a New Strategy to Improve the Cytotoxic Effect of 5-Fluorouracil on Liver Cancer: Impact of Liposomal Composition

Author(s): Saleh Ayed Alanazi*, Gamaleldin Ibrahim Harisa, Mohammad M. Badran, Nazrul Haq, Awwad Abdoh Radwan, Ashok Kumar, Faiyaz Shakeel, Fars Kaed Alanazi*

Journal Name: Current Drug Delivery

Volume 17 , Issue 10 , 2020

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Graphical Abstract:


Purpose: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is 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 as compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect as 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.

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Article Details

Year: 2020
Published on: 29 October, 2020
Page: [898 - 910]
Pages: 13
DOI: 10.2174/1567201817666200211095452
Price: $65

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