Preparation, Characterization, and In Vitro Evaluation of Inclusion Complexes Formed between S-Allylcysteine and Cyclodextrins

Rino Tachikawa; Hiroki Saito; Hajime Moteki; Mitsutoshi Kimura; Hiroaki Kitagishi; Florencio Arce Jr; Gerard Lee See; Takashi Tanikawa; Yutaka Inoue

doi:10.1021/acsomega.2c03489

Preparation, Characterization, and In Vitro Evaluation of Inclusion Complexes Formed between S-Allylcysteine and Cyclodextrins

ACS Omega. 2022 Aug 24;7(35):31233-31245. doi: 10.1021/acsomega.2c03489. eCollection 2022 Sep 6.

Authors

Rino Tachikawa¹, Hiroki Saito², Hajime Moteki², Mitsutoshi Kimura², Hiroaki Kitagishi³, Florencio Arce Jr⁴, Gerard Lee See⁴, Takashi Tanikawa¹, Yutaka Inoue¹

Affiliations

¹ Laboratory of Nutri-Pharmacotherapeutics Management, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Saitama 3500295, Japan.
² Laboratory of Clinical Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Saitama 3500295, Japan.
³ Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, Kyotanabe, Kyoto 6100321, Japan.
⁴ Pharmaceutical Research and Drug Development Laboratories, Department of Pharmacy, School of Health Care Professions, University of San Carlos, Cebu City 6000, The Philippines.

Abstract

The present study prepared inclusion complexes of S-allylcysteine (SAC) and cyclodextrin (α, β, γ) 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/αCD, suggesting a molar ratio of SAC/αCD = 1/1, but no exothermic/endothermic reaction was obtained for the SAC/βCD and SAC/γCD system. Powder X-ray diffraction (PXRD) results showed that the characteristic diffraction peaks of SAC and CDs disappeared in FD (SAC/αCD) and FD (SAC/γCD), indicated by a halo pattern. On the other hand, diffraction peaks originating from SAC and βCDs were observed in FD (SAC/βCD). Near-infrared (NIR) absorption spectroscopy results showed that CH and OH groups derived from SAC and OH groups derived from αCD and γCD cavity were shifted, suggesting complex formation due to intermolecular interactions occurring in SAC/αCD and SAC/γCD. Stability test results showed that the stability was maintained with FD (SAC/αCD) over FD (SAC/βCD) and FD (SAC/γCD). In ¹H-¹H of NOESY NMR measurement, FD (SAC/αCD) 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 αCD cavity. In FD (SAC/γCD), 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 γCD. 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/βCD) inhibited cell proliferation. On the other hand, FD (SAC/αCD) and FD (SAC/γCD) 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.