Preparation, Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 23; p. 7227
• Main Authors: Li, Hui, Zhang, Guolei, Wang, Wei, Chen, Changbao, Jiao, Lili, Wu, Wei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.11.2021; MDPI
• Subjects: Administration, Oral; Bioavailability; Biological Availability; Blood levels; Calorimetry; Calorimetry, Differential Scanning; Cardiomyocytes; Chemical Phenomena; Cyclodextrin; Cyclodextrins; Differential scanning calorimetry; Energy; Fourier transforms; Freeze drying; gamma-Cyclodextrins - chemistry; gamma-Cyclodextrins - pharmacology; Genetic algorithms; ginsenoside Re; Ginsenosides - chemical synthesis; Ginsenosides - chemistry; Ginsenosides - pharmacokinetics; Ginsenosides - pharmacology; Glucose; Hydrogen Bonding; Hydrogen bonds; inclusion complex; Inclusion complexes; Infrared spectroscopy; LC-MS/MS; Molecular docking; Molecular Docking Simulation; molecule docking; Scanning electron microscopy; Simulation; Solubility; Solubility parameters; Spectroscopy, Fourier Transform Infrared; Supramolecular compounds; X ray powder diffraction; X-Ray Diffraction; LC-MS/MS; inclusion complex; ginsenoside Re; molecule docking; bioavailability
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237227

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M (α-CD), 612 M (β-CD), and 14,410 M (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of -4.7 (α-CD), -5.10 (β-CD), and -6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC - of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re's inclusion into γ-CD, and explored the inclusion complex's mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.