Formation and stabilization mechanism of Ginsenoside Rg3 inclusion complexes based on molecular simulation

The formation of inclusion complexes between Ginsenoside Rg3 and cyclodextrins represents a promising strategy to enhance the solubility of G-Rg3. Nevertheless, the molecular mechanisms underlying the interaction between G-Rg3 and cyclodextrins have yet to be fully elucidated. In this study, we employed a combination of molecular simulation and experimental methodologies to identify the most effective solubilizing carriers among G-Rg3, beta-cyclodextrin (beta-CD), 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and 2,6-dimethyl-beta-cyclodextrin (DM-beta-CD). The inclusion complexes formed with HP-beta-CD demonstrates superior stability and water solubility compared to those formed with beta-CD and DM-beta-CD. The preparation process for the inclusion complexes of G-Rg3 and HP-beta-CD was optimized through an orthogonal testing approach. The optimal conditions were determined to be a mass ratio of G-Rg3 to HP-beta-CD of 1:125, an inclusion time of 2 h, and an inclusion temperature of 30 degrees C. The formation of the inclusion complexes was confirmed using DSC, Fourier Transform Infrared FTIR, and XRD techniques. In vitro solubility tests indicated that the solubility of the G-Rg3 inclusion complexes was 2.9 times greater than that of G-Rg3. Molecular dynamics (MD) simulations provided insights into the mechanisms that stabilize the inclusion complexes and enhance their water solubility. The primary interaction force between G-Rg3 and HP-beta-CD was identified as the van der Waals force.