Róka Eszter, Ujhelyi Zoltán, Deli Mária, Bocsik Alexandra, Fenyvesi Éva, Szente Lajos, Fenyvesi Ferenc, Vecsernyés Miklós, Váradi Judit, Fehér Pálma, Gesztelyi Rudolf, Félix Caroline, Perret Florent, Bácskay Ildikó Katalin
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary.
University Lyon 1, ICBMS, Equipe CSAp, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France.
Molecules. 2015 Nov 11;20(11):20269-85. doi: 10.3390/molecules201119694.
Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, the concentration of α-cyclodextrin used may be very high in these cases, and its toxic attributes have to be seriously considered. The objective of this study was to investigate the cytotoxicity of various, differently substituted α-cyclodextrin derivatives and determine relationship between the structures and cytotoxicity. Three different methods were used, viability tests (MTT assay and Real Time Cell Electronic Sensing on Caco-2 cells) as well as hemolysis test on human red blood cells. The effect of α-cyclodextrin derivatives resulted in concentration-dependent cytotoxicity, so the IC50 values have been determined. Based on our evaluation, the Real Time Cell Electronic Sensing method is the most accurate for describing the time and concentration dependency of the observed toxic effects. Regarding the cytotoxicity on Caco-2 cells, phosphatidylcholine extraction may play a main role in the mechanism. Our results should provide help in selecting those α-cyclodextrin derivatives which have the potential of being used safely in medical formulations.
环糊精，即使是六元的α-环糊精，在各种药典中也被批准作为药物辅料用于增溶和稳定药物以及控制药物释放。最近，α-环糊精也作为对血脂谱有有益作用的健康食品上市。然而，在这些情况下使用的α-环糊精浓度可能非常高，其毒性特性必须得到认真考虑。本研究的目的是研究各种不同取代的α-环糊精衍生物的细胞毒性，并确定结构与细胞毒性之间的关系。使用了三种不同的方法，即活力测试（MTT 法和对 Caco-2 细胞的实时细胞电子传感）以及对人红细胞的溶血试验。α-环糊精衍生物的作用导致浓度依赖性细胞毒性，因此已确定 IC50 值。根据我们的评估，实时细胞电子传感方法在描述观察到的毒性作用的时间和浓度依赖性方面最为准确。关于对 Caco-2 细胞的细胞毒性，磷脂酰胆碱提取可能在其机制中起主要作用。我们的结果应有助于选择那些有潜力在药物制剂中安全使用的α-环糊精衍生物。
