Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects

Abstract

Hong Jiang,1,* Zhi-Peng Li,1,* Gui-Xiang Tian,1,* Rui-Yan Pan,1 Chong-Mei Xu,2 Bo Zhang,2 Jing-liang Wu1 1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, China *These authors contributed equally to this work Background: Recent efforts have been focused on combining two or more therapeutic approaches with different mechanisms to enhance antitumor therapy. Moreover, nanosize drug-delivery systems for codelivering two drugs with proapoptotic and antiangiogenic activities have exhibited great potential in efficient treatment of cancers. Methods: Glycyrrhetinic acid (GA)–modified liposomes (GA LPs) for liver-targeted codelivery of curcumin (Cur) and combretastatin A4 phosphate (CA4P) were prepared and characterized. In vitro cellular uptake, cytotoxicity, cell migration, in vivo biodistribution, antitumor activity, and histopathological studies were performed. Results: Compared with unmodified LPs (Cur-CA4P LPs), Cur-CA4P/GA LPs were taken up effectively by human hepatocellular carcinoma cells (BEL-7402) and showed higher cytotoxicity than free drugs. In vivo real-time near-infrared fluorescence–imaging results indicated that GA-targeted LPs increased accumulation in the tumor region. Moreover, Cur-CA4P/GA LPs showed stronger inhibition of tumor proliferation than Cur, Cur + CA4P, and Cur-CA4P LPs in vivo antitumor studies, which was also verified by H&E staining. Conclusion: GA-modified LPs can serve as a promising nanocarrier for liver-targeted co-delivery of antitumor drugs against hepatocellular carcinoma. Keywords: liver-targeted, LPs, curcumin, combretastatin A4 phosphate, combination therapy

Keywords

• Liver-targeted
• LPs
• curcumin
• combretastatin A4 phosphate
• combination therapy