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

• Published in: International journal of pharmaceutics 2015-12, Vol.496 (2), p.896-902
• Main Authors: Stelzl, Dominik, Nielsen, Thorbjørn Terndrup, Hansen, Terkel, di Cagno, Massimiliano
• Format: Article
• Language: English
• Subjects: beta-Cyclodextrins - chemistry; Cholesterol - isolation & purification; Cholesterol depletion; Dextrans - chemistry; Giant unilamellar vesicles; Lipid Bilayers - analysis; Phospholipids - analysis; Safe-toxicity studies; Solubility; β-cyclodextrin-dextran polymers; β-cyclodextrins
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.10.041

[Display omitted] 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.