Galactose Modified Liposomes for Effective Co-Delivery of Doxorubicin and Combretastatin A4

Abstract

Bo Lian,1,* Hua Wei,2,* Ruiyan Pan,3,* Jingui Sun,4 Bo Zhang,3 Jingliang Wu,1 Xiujie Li,1 Guixiang Tian1 1School of Bioscience and Technology, Weifang Medical University, Weifang 261053, People’s Republic of China; 2Department of Endocrinology, ShouGuang Peoples’ Hospital, Weifang 262700, People’s Republic of China; 3School of Pharmacy, Weifang Medical University, Weifang 261053, People’s Republic of China; 4Department of Oncology, ShouGuang Peoples’ Hospital, Weifang 262700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiujie Li Email [email protected] TianSchool of Bioscience and Technology, Weifang Medical University, Weifang 261053, People’s Republic of ChinaEmail [email protected]: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to enhance antitumor therapy.Methods: In this study, galactose-modified liposomes (Gal-LPs) were prepared for co-delivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice.Results: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity.Conclusion: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.Keywords: liposomes, anti-hepatoma, co-delivery, combination therapy

Keywords

• liposomes
• anti-hepatoma
• co-delivery
• combination therapy