Enhancement of bioavailability and anti-inflammatory activity of inotodiol through complexation with -cyclodextrin

The aims of the present study were to fabricate an inclusion complex of inotodiol (INO) with cyclodextrin (CD) and to evaluate its bioavailability and anti-inflammatory activity. Different types of cyclodextrins in DDW were employed as host molecules, and INO dissolved in ethanol was added to the CD solutions during ultra-sonication. DSC and FTIR results showed that INO was complexed only with gamma-cyclodextrin (gamma-CD) efficiently at a molar ratio of 1:3 (INO1/gamma-CD3). Large mean particle size (261.4 nm), high polydispersity index (0.497), and bimodal size distribution of INO1/gamma-CD3 resulted from the formation of large aggregates after the inclusion complex formation. Following oral administration at the dose of 1.0 mg/kg for INO1/gamma-CD3 group and the 2.0 mg/kg for INO group in mouse, the maximum inotodiol plasma concentration (C-max) and the relative area under curve (AUC per 1 mg/kg dose) were 2.6- and 4.96-fold higher, respectively, in the INO1/gamma-CD3 group than in the INO group. Anti-inflammatory activity analysis of INO was conducted using RAW264.7 cells stimulated by lipopolysaccharide, and the repression effect of INO on pro-inflammatory cytokines was enhanced by the complexation with gamma-CD. Our findings suggest that INO1/gamma-CD3 can be a potent therapeutic formulation for the treatment of inflammatory diseases.