Maltosyl-β-cyclodextrin mediated SupramolecularHost-Guest inclusion complex used for enhancing baicalin antioxidant activity and bioavailability

Abstract Baicalin (BCL) is a flavonoid compound with demonstrated potential therapeutic benefits, but the clinical advancements are limited mainly due to its poor aqueous solubility. A guest-host supermolecular inclusion complex of mono-6-O-α-maltosyl-β-cyclodextrin (G2-β-CD) with BCL was developed to improve the aqueous solubility of BCL. The resultant inclusion complex was characterized by DSC, FT-IR, P-XRD, 1HNMR, 2D-ROESY and SEM analysis. Solubility test suggested that G2-β-CD markedly improved the solubility of BCL and showed AL type phase diagrams. The spectral shifts suggested that the phenyl moiety is buried deeper than the chromen moiety and protrudes from the 6-hydroxyl side of G2-β-CD. Molecular docking verified the experimental findings and supported the insertion of benzene ring of BCL into G2-β-CD cavity via hydrophobic interactions and possible hydrogen bonds. The enhanced bioavailability of the inclusion complex was reflected in earlier Tmax, higher Cmax and larger AUC0-∞ than that of BCL after its oral administration. Taken together, these findings suggested that the solid inclusion complex BCL-G2-β-CD may serve as valuable BCL solid dosage form with good solubility and dissolution rate.