Formulation and Evaluation on Synergetic Anti-Hepatoma Effect of a Chemically Stable and Release-Controlled Nanoself-Assembly with Natural Monomers

Lanlan Zong,1,* Yanling Wang,1,* Shiyu Song,1 Huiqi Zhang,1 Shengcai Mu,1 Wenshang Liu,1 Yu Feng,1 Shumin Wang,1 Ziwei Tu,1 Qi Yuan,1 Luhui Li,2 Xiaohui Pu1 1School of Pharmacy and Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 2Medical school, Henan Technical Institute, Kaifeng, Henan, 475004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Yuan; Xiaohui Pu, Tel/Fax +86-371-23880680, Email kaifengYQ2017@163.com; pgh425@163.comIntroduction: Hepatoma is the leading cause of death among liver diseases worldwide. Modern pharmacological studies suggest that some natural monomeric compounds have a significant effect on inhibiting tumor growth. However, poor stability and solubility, and side effects are the main factors limiting the clinical application of natural monomeric compounds.Methods: In this paper, drug-co-loaded nanoself-assemblies were selected as a delivery system to improve the chemical stability and solubility of Tanshinone II A and Glycyrrhetinic acid, and to produce a synergetic anti-hepatoma effect.Results: The study suggested that the drug co-loaded nanoself-assemblies showed high drug loading capacity, good physical and chemical stability, and controlled release. In vitro cell experiments verified that the drug-co-loaded nanoself-assemblies could increase the cellular uptake and cell inhibitory activity. In vivo studies verified that the drug co-loaded nanoself-assemblies could prolong the MRT0-∞, increase accumulation in tumor and liver tissues, and show strong synergistic anti-tumor effect and good bio-safety in H22 tumor-bearing mice.Conclusion: This work indicates that natural monomeric compounds co-loaded nanoself-assemblies would be a potential strategy for the treatment of hepatoma.Graphical Abstract: Keywords: nanoself-assemblies, drug combination, glycyrrhetinic acid, tanshinone IIA, liver cancer