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

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• 作者：Dominik Stelzl^a ; ^b ; Thorbjø ; rn Terndrup Nielsen^c ; Terkel Hansen^d ; Massimiliano di Cagno^a ; ^{massimiliano.p.cagno@uit.no" class="auth_mail" title="E-mail the corresponding author}
• 关键词：β-cyclodextrins ; β-cyclodextrin-dextran polymers ; Cholesterol depletion ; Safe-toxicity studies ; Giant unilamellar vesicles
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：30 December 2015
• 年：2015
• 卷：496
• 期：2
• 页码：896-902
• 全文大小：877 K

文摘

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.