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

Authors Lian B, Wei H, Pan R, Sun J, Zhang B, Wu J, Li X, Tian G

Received 28 September 2020

Accepted for publication 1 December 2020

Published 15 January 2021 Volume 2021:16 Pages 457—467

DOI https://doi.org/10.2147/IJN.S283793

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Farooq A. Shiekh


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 work

Correspondence: Xiujie Li Email lixiujie@wfmc.edu.cn
Guixiang Tian
School of Bioscience and Technology, Weifang Medical University, Weifang 261053, People’s Republic of China
Email gxtian2008@163.com

Background: 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

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