Structural analysis and cytotoxicity of host-guest inclusion complexes of cannabidiol with three native cyclodextrins

Abstract The preparation of inclusion complex is often used to improve the physicochemical properties of poorly soluble drugs. In this work, we successfully prepared inclusion complexes of cannabidiol (CBD) with three native cyclodextrins by suspension method, respectively named α-cyclodextrins (α-CD), β-cyclodextrins (β-CD), and γ-cyclodextrins (γ-CD). Many methods including 1 H and 2D NMR analysis, X-ray power diffraction (XRD), scanning electron microscopy (SEM) analysis and thermal gravimetric analysis (TGA) were used to characterize the inclusion behaviors of the inclusion complexes of cannabidiol with cyclodextrins both in solution and solid forms. The results indicated that cannabidiol were encapsulated within the cavity of α-CD, β-CD and γ-CD to form a 1:1, 2:1 and 2:1 host-guest inclusion complex, and possible inclusion modes of cannabidiol with three CDs were speculated. The water solubility and in vitro cytotoxicity of the inclusion complexes were respectively evaluated by the methods of saturated solution and MTT additionally. It is noteworthy that significant increases in the water solubility and in vitro cytotoxicity of cannabidiol were found in the form of inclusion complex with three natural cyclodextrins compared with free cannabidiol.