b-CD-dextran polymer for efficient sequestration of cholesterol from phospholipid bilayers: Mechanistic and safe-toxicity investigations

In this work we investigated the suitability of β-cyclodextrin-dextran (BCD-dextran) polymer as cholesterol sequestering agent in vitro to evaluate their suitability as a new possible iv treatment for hypercholesterolemia. BCD-dextran-cholesterol complexation was investigated by phase solubility studies as well as employing an in vitro model based on cholesterol reach-giant unilamellar vesicles (GUVs). Subsequently, BCD-dextran were also applied to two different cell lines (RAMOS and MRC5) and results were correlated to cells toxicity. Results can be summarized as follows: a) BCD-dextran polymer are capable of extracting significant amount of cholesterol and cholesteryl esters from phospholipid bilayers; b) BCD-dextran sequesters cholesterol from both RAMOS and MRC5 cell lines to a higher extend in comparison to standard BCDs; c) BCD-dextran results of lower cytotoxicity in comparison to standard BCDs (especially in comparison to methyl-β-CD) on both cell lines. In conclusion, BCD-dextran results an extremely efficient cholesterol-sequestering agent preserving livability of cells up to a concentration of 1 mM. This phenomenon might play a key role for the development of a new and efficient iv treatment for hypercholesterolemia.