Preparation, Characterization, and In Vitro Evaluation of Inclusion Complexes Formed between <i>S</i>-Allylcysteine and Cyclodextrins
Rino Tachikawa, Hiroki Saito, Hajime Moteki, Mitsutoshi Kimura, Hiroaki Kitagishi, Florencio Arce, Gerard Lee See, Takashi Tanikawa, Yutaka Inoue
Abstract
The present study prepared inclusion complexes of Sallylcysteine (SAC) and cyclodextrin (, , ) by the freeze-drying (FD) method and verified the inclusion behavior of the solid dispersion. Also, the study investigated the effect of SAC/CD complex formation on liver tumor cells. Isothermal titration calorimetry (ITC) measurements confirmed the exothermic titration curve for SAC/CD, suggesting a molar ratio of SAC/ CD = 1/1, but no exothermic/endothermic reaction was obtained for the SAC/CD and SAC/CD system. Powder X-ray diffraction (PXRD) results showed that the characteristic diffraction peaks of SAC and CDs disappeared in FD (SAC/CD) and FD (SAC/CD), indicated by a halo pattern. On the other hand, diffraction peaks originating from SAC and CDs were observed in FD (SAC/CD). Near-infrared (NIR) absorption spectroscopy results showed that CH and OH groups derived from SAC and OH groups derived from CD and CD cavity were shifted, suggesting complex formation due to intermolecular interactions occurring in SAC/CD and SAC/CD. Stability test results showed that the stability was maintained with FD (SAC/CD) over FD (SAC/CD) and FD (SAC/CD). In 1 H-1 H of NOESY NMR measurement, FD (SAC/CD) was confirmed to have a cross peak at the CH group of the alkene of SAC and the proton (H-3, -5, -6) in the CD cavity. In FD (SAC/CD), a cross peak was confirmed at the alkyl group on the carbonyl group side of SAC and the proton (H-3) in the cavity of CD. From the above, it was suggested that the inclusion mode of SAC is different on FD (SAC/CDs). The results of the hepatocyte proliferation inhibition test using HepG2 cells showed that FD (SAC/CD) inhibited cell proliferation. On the other hand, FD (SAC/CD) and FD (SAC/CD) did not show a significant decrease in the number of viable cells. These results suggest that the difference in the inclusion mode may contribute to the stability and cell proliferation inhibition.