Interactions of cholesterol with cyclodextrins in aqueous solution

Abstract

The interaction of cholesterol with several cyclodextrins (CDs) was investigated in water using solubility method. It was found that heptakis (2,6-di-O-methyl)-β-CD (DOM-β-CD) forms two types of soluble complex, with molar ratios of 1:1 and 1:2 (cholesterol:DOM-β-CD), and neither a soluble nor insoluble complex is formed between cholesterol and α-CD, β-CD, and γ-CD, although a minor soluble complex formation was observed between cholesterol and 2-hydroxylpropyl-β-CD. The thermodynamic parameters for 1:1 and 1:2 complex formation of cholesterol with DOM-β-CD obtained from the changes in K with temperature are as follows: ΔG°1:1=-11.6 kJ/mol at 25°C (K1:1=1. 09×102 M-1); ΔH°1:1=-3.38 kJ/mol; TΔS°1:1=8.25 kJ/mol; ΔG°1:2=- 27.1 kJ/mol at 25°C (K1:2=5.68×104 M -1); ΔH°1:2=-3.96 kJ/mol; and TΔS°1:2=23.2 kJ/mol. The formation of the 1:2 complex occurred much more easily than that of the 1:1 complex. The driving force for 1:1 and 1:2 complex formation was considered to be mainly hydrophobic interaction. Also, based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structutures of the 1:2 complex were estimated. © 2003 Pharmaceutical Society of Japan.