Preparation of Liver-targeted Nano-prodrug Based on Sodium Alginate Derivative and the Study on Antitumor Activity†

Abstract

The high viscosity of sodium alginate( ALG) causes its insufficient targeted ligand loading,and further influences the targeted recognition effect of nano-prodrug. Here,oligomeric ethylene glycol modified-sodium alginate( ALG-mOEG) was used as a carrier to improve the targeted-ligands loading. Results showed that ALG-mOEG significantly improved glycyrrhetinic acid( GA) loading compared with unmodified ALG( 11. 8%vs. 6. 9%,1. 97-fold increase). On this basis,the liver targeted nano-prodrug( DOX-ALG-mOEG /GA-ALGmOEG NPs) was self-assembled via dialysis method by mixing GA-ALG-mOEG and DOX-ALG-mOEG. Cell cytotoxicity experiment showed that DOX-ALG-mOEG /GA-ALG-mOEG NPs inhibited HepG2 proliferation with an half maximal inhibitory concentration( IC50) value of 58.1 ng/mL while the IC50 of control group was141. 7 ng /mL; the tumor growth inhibition rate( IR) reached to 88. 4%,improved by 11. 5% compared to that of the control group. This study show that the liver targeted nano-prodrug based on ALG-mOEG can effectively improve the drug utilization,and provide a reference for the preparation of other polysaccharide targeted nanoprodrug.