Inclusion complex of emodin and glycyrrhetinic acid-conjugated-β-cyclodextrin to target liver cells: synthesis, characterization, and bioactivity in vitro and in vivo

Abstract

The objective of this study is to prepare a novel delivery vector, glycyrrhetinic acid -conjugated-β-cyclodextrin (GA-CD) for liver targeting, and investigate the effects of the emodin-GA-CD inclusion complex (E-GA-CD complex) on liver cancer therapy. GA-CD was synthesized from GA and CD, and was used to encapsulate emodin to form an E-GA-CD complex. Proton nuclear magnetic resonance spectroscopy, two-dimensional rotating-frame Overhauser effect spectroscopy, and differential scanning calorimetry were used to characterize GA-CD and the E-GA-CD complex. Liver cell targeting bioactivity of the E-GA-CD complex was investigated by cellular uptake, cell viability, and biodistribution. In vitro results revealed that the E-GA-CD complex exhibited increased cellular uptake and cytotoxicity against Hep3B cells compared to free emodin. In vivo biodistribution results indicated that mice treated with the E-GA-CD complex exhibited greater emodin uptake in liver tissue than emodin-treated mice, suggesting that the E-GA-CD complex was effective in targeting liver cells.