Investigation of the influence of β-cyclodextrin on cholesterol lodgement - A molecular dynamics simulation study

The search for new methods to remove the excess cholesterol molecules, precursors of plaque deposition in an early phase of atherosclerosis disease, is a vital subject of molecular medicine and our studies are related to this issue. The cyclodextrins have already been used in pharmaceutical industry mainly as complexing agents to increase the aqueous solubility of poorly water-soluble drugs, and to increase their bioavailability and stability. The cavity diameter of beta-cyclodextrin molecule has been found to be the most appropriate size for hormones, vitamins, and other compounds frequently used in tissue and cell culture applications. Using the molecular dynamics simulation method we studied the system composed of beta-cyclodextrin (beta CD) molecules and cholesterol clusters, both standalone and in a water environment. We found that two configurations of beta CD-cholesterol complexes appear. The occurrence of the particular complex configuration is strongly related to the presence of water environment. We have found that beta CD molecules do not penetrate the interior of cholesterol cluster, rather stick or "glue" to these cholesterol molecules that make up the surface of the cluster. Moreover, our simulations have shown that the ability of beta CD to pull cholesterol molecule out of the cluster surface is rather limited. Consequently, some chemical modifications of beta-cyclodextrin molecule should be considered while searching for the oligosaccharide based tools (nanomedicine) able to effectively influence cholesterol deposit in the inner part of blood arteries. (C) 2018 Elsevier B.V. All rights reserved.