title: Competition between self-inclusion and drug binding explains the pH dependence of the cyclodextrin drug carrier - molecular modelling and electrochemistry studies.
abstract: A non-toxic lipoic acid derivative of β cyclodextrin (βCDLip) with an electron-rich aromatic linker was studied as a carrier for the drug doxorubicin with the aim of decreasing the toxic side effects of this drug. The modified cyclodextrin strengthened the drug binding and differentiated the complex-forming ability with dependence on pH. The stability constants of the complexes were evaluated by voltammetry and spectrofluorometry. Molecular modelling provided deeper insight into the nature of the ligand structure itself and the drug-ligand interactions, showing the different contributions of the self-inclusion of the ligand substituent at different pH values. As a result, the modes of interaction of βCDLip with the drug and factors affecting the stabilities of the complex under the pH conditions of healthy and tumour cells could be discovered and explained.
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura 1 02-093 Warsaw, Poland. bilewicz@chem.uw.edu.pl.
authors.forename: Olga
authors.initials: O
authors.lastname: Swiech
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura 1 02-093 Warsaw, Poland. bilewicz@chem.uw.edu.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Majdecki
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura 1 02-093 Warsaw, Poland. bilewicz@chem.uw.edu.pl.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Debinski
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura 1 02-093 Warsaw, Poland. bilewicz@chem.uw.edu.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Krzak
authors.affiliation: Department of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, Warsaw, 03-195, Poland. m.kruszewski@ichtj.waw.pl.
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Stępkowski
authors.affiliation: Department of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, Warsaw, 03-195, Poland. m.kruszewski@ichtj.waw.pl.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wójciuk
authors.affiliation: Faculty of Medicine, University of Information Technology and Management in Rzeszów, ul. Sucharskiego 2, Rzeszów, 35-225, Poland. m.kruszewski@ichtj.waw.pl and Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, Lublin, 20-090, Poland. m.kruszewski@ichtj.waw.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: University of Warsaw, Faculty of Chemistry, Pasteura 1 02-093 Warsaw, Poland. bilewicz@chem.uw.edu.pl.
authors.forename: Renata
authors.initials: R
authors.lastname: Bilewicz
mesh_terms: D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D055664:Electrochemical Techniques; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008063:Thioctic Acid / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D047392:beta-Cyclodextrins; D008063:Thioctic Acid; D004317:Doxorubicin