Inclusion complex of GA-13315 with cyclodextrins: preparation, characterization, inclusion mode and properties

GA-13315 (13-chlorine-3,15-dioxy-gibberllic acid methyl ester) was semi-synthesized by GA3 (gibberellic acid) as a potential anticancer drug. To pursue its promising application, cyclodextrin was used for forming complexes to overcome its drawbacks such as poor water solubility and stability. So, GA-13315/CD complexes were prepared with native β-cyclodextrin and its derivatives (hydroxypropyl-β-cyclodextrin (HPβCD)) and their inclusion complexation behavior, characterization and binding ability in both solution and the solid state was studied by means of UV, XRD, DSC, SEM, (1)H and 2D NMR spectroscopy. Furthermore, preliminary in vitro cytotoxicity assay showed that the complexes still maintain antitumor activities, compared with GA-13315 or adriamycin (ADM, positive control) as the positive control. The results showed that the water solubility and stability of GA-13315 were obviously improved in the inclusion complex with cyclodextrins, suggesting the inclusion complexes as promising future therapeutic agents.