title: Evaluation of the Cytotoxicity of α-Cyclodextrin Derivatives on the Caco-2 Cell Line and Human Erythrocytes.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. roka.eszter@pharm.unideb.hu.|University Lyon 1, ICBMS, Equipe CSAp, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France. roka.eszter@pharm.unideb.hu.
authors.forename: Eszter
authors.initials: E
authors.lastname: Róka
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. ujhelyi.zoltan@pharm.unideb.hu.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ujhelyi
authors.affiliation: Department of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. deli.maria@brc.mta.hu.
authors.forename: Mária
authors.initials: M
authors.lastname: Deli
authors.affiliation: Department of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary. bocsik@brc.hu.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bocsik
authors.affiliation: Cyclolab Ltd., Illatos út 7, Budapest H-1097, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Fenyvesi
authors.affiliation: Cyclolab Ltd., Illatos út 7, Budapest H-1097, Hungary. szente@cyclolab.hu.
authors.forename: Lajos
authors.initials: L
authors.lastname: Szente
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. fenyvesi.ferenc@pharm.unideb.hu.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Fenyvesi
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. vecsernyes.miklos@pharm.unideb.hu.
authors.forename: Miklós
authors.initials: M
authors.lastname: Vecsernyés
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. varadi.judit@pharm.unideb.hu.
authors.forename: Judit
authors.initials: J
authors.lastname: Váradi
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. feher.palma@pharm.unideb.hu.
authors.forename: Pálma
authors.initials: P
authors.lastname: Fehér
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. gesztelyi.rudolf@pharm.unideb.hu.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.affiliation: University Lyon 1, ICBMS, Equipe CSAp, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France. caroline.felix@univ-lyon1.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Félix
authors.affiliation: University Lyon 1, ICBMS, Equipe CSAp, 43 Boulevard du 11 Novembre 1918, Villeurbanne F-69622, France. florent-perret@univ-lyon1.fr.
authors.forename: Florent
authors.initials: F
authors.lastname: Perret
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei körút 98, Debrecen H-4032, Hungary. bacskay.ildiko@pharm.unideb.hu.
authors.forename: Ildikó Katalin
authors.initials: IK
authors.lastname: Bácskay
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D047391:alpha-Cyclodextrins / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin
keywords: Caco-2 cell line; RT-CES; cytotoxicity; hemolysis; α-CD derivatives