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Optimized formulation of multivesicular liposomes loaded with oleanolic acid enhanced anticancer effect in vitro

Authors Wang Y, Luo Y, Li C, Zhang X, Pi C, Yu L, Wang S, Zhong Z

Received 26 November 2016

Accepted for publication 1 March 2017

Published 27 March 2017 Volume 2017:11 Pages 955—968

DOI https://doi.org/10.2147/DDDT.S128795

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Professor Jianbo Sun

Yunlong Wang,1,* Yuling Luo,1,* Chunhong Li,1 Xiaoqin Zhang,1 Chao Pi,1 Lu Yu,2 Shurong Wang,1 Zhirong Zhong1

1Department of Pharmaceutical Sciences, School of Pharmacy, 2Department of Chemistry, The Institute of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Abstract: Invasion and metastasis are the main causes leading to the death of patients with hepatocellular carcinoma (HCC). Multivesicular liposomes loaded with oleanolic acid (OA-MVLs) have been well demonstrated to suppress survival, growth and angiogenesis of HCC cells. Emerging evidence demonstrates that OA was able to suppress the invasion of HCC cells by down-regulating myocyte enhancer factor-2. We hypothesized that the optimized OA-MVLs could inhibit the migration and invasion of HCC cells. In this study, we utilized central composite design and response surface methodology to assess the influence of some parameters on particle size and encapsulation efficiency and obtain the optimized formulation of OA-MVLs. Subsequently, the human HCC cell lines SMMC-7721 and HepG2 were treated with different doses of OA-MVLs and OA, respectively. Cellular survival, adhesion, migration and invasion in vitro were evaluated. We found that the optimized OA-MVLs significantly decreased the ability of HCC cells to adhere, migrate and invade in vitro. Furthermore, OA-MVLs significantly inhibited the survival of HCC cells at 160 µmol/L but showed no obvious inhibition effect on the cell vitality of normal liver cells. Our findings indicate that OA-MVLs did inhibit the cell survival, adhesion, invasion and metastasis of HCC cells in vitro. Although the involved mechanisms are still unclear, our findings can contribute to a better development of a preventive and therapeutic strategy for human HCC.

Keywords: oleanolic acid, multivesicular liposomes, central composite design, adhesion, invasion, migration

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