title: β-CD-dextran polymer for efficient sequestration of cholesterol from phospholipid bilayers: Mechanistic and safe-toxicity investigations.
abstract: The aim of this work was to investigate the suitability of β-cyclodextrin-dextran (BCD-dextran) polymer as cholesterol sequestering agent in vitro. For this purpose, BCD-dextran-cholesterol complexation was studied by phase solubility studies as well as with a specifically designed in vitro model based on giant unilamellar vesicles (GUVs) to evaluate the ability of this polymer to sequestrate cholesterol from phospholipid bilayers. Cholesterol-sequestering ability of BCD-dextran was also investigated on different cell lines relevant for the hematopoietic system and results were correlated to cells toxicity. BCD-dextran polymer was capable of extracting significant amount of cholesterol from phospholipid bilayers and to a higher extent in comparison to available β-cyclodextrins (BCDs). The ability of BCD-dextran in sequestering cholesterol resulted also very high on cell lines relevant for the hematopoietic system. Moreover, BCD-dextran resulted less toxic on cell cultures due to higher selectivity in sequestering cholesterol in comparison to MBCD (that sequestrated also significant amounts of cholesteryl esters). In conclusion, BCD-dextran resulted an extremely efficient cholesterol-sequestering agent and BCD-dextran resulted more selective to cholesterol extraction in comparison to other BCDs (therefore of lower cytotoxicity). This phenomenon might play a key role to develop an efficient treatment for hypercholesterolemia based on cholesterol segregation.
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; Department of Applied Life Sciences, University of Applied Sciences, FH Campus Wien, Vienna, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Stelzl
authors.affiliation: Department of Chemistry and Biosciences, Aalborg University, Aalborg, Denmark.
authors.forename: Thorbjørn Terndrup
authors.initials: TT
authors.lastname: Nielsen
authors.affiliation: Natural Products and Medicinal Chemistry Research Group, Department of Pharmacy, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Terkel
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Electronic address: massimiliano.p.cagno@uit.no.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: di Cagno
mesh_terms: D002784:Cholesterol / Q000302:isolation & purification*; D003911:Dextrans / Q000737:chemistry*; D008051:Lipid Bilayers / Q000032:analysis*; D010743:Phospholipids / Q000032:analysis*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003911:Dextrans; D008051:Lipid Bilayers; D010743:Phospholipids; D047392:beta-Cyclodextrins; D002784:Cholesterol
keywords: Cholesterol depletion; Giant unilamellar vesicles; Safe-toxicity studies; β-cyclodextrin-dextran polymers; β-cyclodextrins