Preparation, characterization, and physicochemical property of the inclusion complexes of Cannabisin A with β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Cannabisin A (CA), derived from hemp seed shells, has antioxidant and anti-neuroinflammatory activity. However, its application is limited due to its poor solubility. In this work, β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-) were used to encapsulate CA to increase its water-solubility. The inclusion complexes of CA with β-CD (CA/β-CD IC) and the inclusion complexes of CA with HP-β-CD (CA/HP-β-CD IC) were prepared by the aqueous ethanol solution method. The Job's plot assay and Phase solubility assay revealed that the inclusion complexes of CA with β-CD/HP-β-CD formed at a 1:1 stoichiometric ratio. However, considering the inclusion process is reversible, the inclusion complexes were prepared at a 1:2 molar ratio. The structure of the inclusion complexes was identified by FT-IR, XRD, DSC, SEM, and NMR. In addition, the results of 1H NMR, 2D ROESY NMR, and molecular docking further determined the possible conformations of the inclusion complexes. The solubility of the CA in the CA/β-CD IC and CA/HP-β-CD IC was increased by 13.95-fold and 56.37-fold, respectively, compared to pure CA; and the dissolution and antioxidant activity of the CA were also significantly promoted after complexation. This study proved that CA/HP-β-CD IC was the preferred inclusion complex compared to CA/β-CD IC due to its better physicochemical properties.