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.