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Construction of Redox-sensitive Liposomes Modified by Glycyrrhetinic Acid and Evaluation of Anti-hepatocellular Carcinoma Activity.

Jie Hu,Yongsheng Zheng,Zhi-guang Wen,Hudie Fu,Xue-sen Yang,Xuexin Ye,Shengpeng Zhu,Li Kang,Xiaojun Li,Xinzhou Yang,Yan Hu

Published 2023 in Chemistry and Physics of Lipids

ABSTRACT

The aim of this study was to construct a bifunctional liposome with hepatic-targeting capacity by modifying with a targerting ligand and an intracellular tumor reduction response functional group to deliver drugs precisely to focal liver tissues and release them in large quantities in hepatocellular carcinoma cells. This could improve drug efficacy and reduce toxic side effects at the same time. First, the bifunctional ligand for lipsome was successfully obtained by chemically synthesizing it from the hepatic-targeting glycyrrhetinic acid (GA) molecule, cystamine, and the membrane component cholesterol. The ligand was then used to modify the curcumin liposomes. The particle size, and zeta potential of the liposomes were determined with a nanoparticle sizer, and the morphology was observed by transmission electron microscopy. The encapsulation rate and drug release behavior were also determined. Further, the in vitro stability of the liposomes and the changes in the simulated reducing environment were determined. Finally, the in vitro antitumor activity and cellular uptake efficiency of the drug-loaded liposomes were investigated by performing cellular assays. The results showed that the prepared liposomes had a uniform particle size of 143.6±2.86nm with good stability and an encapsulation rate of 84.3±2.1%. Moreover, the particle size of the liposomes significantly increased and the structure was destroyed in a DTT reducing environment. Cellular experiments showed that the modified liposomes had better cytotoxic effects on hepatocarcinoma cells than both normal liposomes and free drugs. This study has great potential for tumor therapy and provides new ideas for the clinical use of oncology drugs in dosage forms.

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