Inclusion complexation of emodin with various β-cyclodextrin derivatives: Preparation, characterization, molecular docking, and anticancer activity

Encapsulation with beta-cyclodextrin (beta CD) has primarily been used to enhance the solubility of lipophilic guest molecules. Emodin (ED) stands out for its profound biological properties, especially anticancer activity. However, its usage in pharmaceutical applications has been hindered by its poor aqueous solubility. In the present work, we performed inclusion complexation of ED with beta CD and its derivatives: hydroxypropyl-beta-cyclodextrin (HP beta CD), sulfobutylether-beta-cyclodextrin with degree of substitution (DS) of 2 (SBE2 beta CD) and 6.0-7.1 (SBE7 beta CD) and 2,6-di-O-methyl-beta-cyclodextrin (DM beta CD), to identify the most promising drug carrier to enhance the water solubility and the anticancer activity of ED. The AL-type phase solubility diagram indicates 1:1 stoichiometry between ED and beta CDs. The ED/DM beta CD complex shows the highest stability (K-C = 3800 M-1) and the highest water solubility (113.86 mu g/mL) at 30 degrees C, followed by ED/SBE7 beta CD, ED/HPBCD, ED/SBE2 beta CD, and ED/beta CD complexes. The SEM micrographs and DSC thermograms confirmed the inclusion complex formation between host and guest by attaining new surface morphological structures and thermal behaviors, respectively. Molecular docking suggests C-form insertion as the preferred binding mode of ED toward beta CDs. Interestingly, the anti-proliferative effect on KKU-213A, KKU-213B, A549, and H1975 cancer cell lines of inclusion complexes, especially ED/DM beta CD, ED/SBE7 beta CD, and ED/HP beta CD, was significantly higher than that of ED alone. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Encapsulation with beta-cyclodextrin (β-CD) has been explored to enhance the solubility of emodin (ED) for pharmaceutical applications. In this study, inclusion complexation of ED with β-CD and its derivatives was performed to identify the most promising drug carrier. The ED/DM-β-CD complex showed the highest stability and water solubility, followed by ED/SBE7-β-CD and ED/HP-β-CD complexes. The SEM micrographs and DSC thermograms confirmed the inclusion complex formation, and molecular docking suggested C-form insertion as the preferred binding mode. Moreover, the inclusion complexes, especially ED/DM-β-CD, showed significantly higher anti-proliferative effects on cancer cell lines compared to ED alone.