Preparation, characterization and cytotoxic evaluation of inclusion complexes between celastrol with polyamine-modified β-cyclodextrins

Celastrol (CSL), the major constituent from traditional Chinese medicine Tripterygium wilfordii Hook, has attracted considerable interest in the medicinal society due to its multiple biological activities. However, poor solubility and obvious toxic side effect have limited its application in the pharmaceutical field. To address the problems, the inclusion complexes of mono polyamine-modified beta-CD (H1) and the polyamine-brideged bis(beta-CD) (H2) with CSL were prepared. The characterization of inclusion complexes was investigated by NMR, XRD FT-IR and SEM, and the binding behaviors of H1-2 with CSL were investigated by UV. The results showed that the H2 gave the binding constant (Ks) towards CSL up to 1.7 times higher than that of H1, through cooperative binding of two hydrophobic CD cavities with one guest. Remarkably, complexation with H1 and H2 improved CSL solubility in water from 0.044 mg/mL up to 2.31 and 2.68 mg/mL, respectively. The in vitro anticancer activity of H1/CSL inclusion complex was better than that of cisplatin (positive control). Meanwhile, the toxicity of CSL was slightly reduced after the formation of the inclusion complex with H1. Therefore, the complexes of CSL with H1-2 favor their use in anticancer drug formulations, broadening the field of application in clinic. [GRAPHICS] .