Gutay-Toth Z.,Debrecen University |
Fenyvesi F.,Debrecen University |
Barsony O.,Debrecen University |
Szente L.,Development Laboratory Ltd. |
And 3 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2016
The 15D3 mouse monoclonal antibody (mAb) binds an uncharacterized extracellular epitope of the ATP Binding Cassette (ABC) transporter human P-glycoprotein (Pgp). Depletion of cell plasma membrane cholesterol by using methyl-β-cyclodextrin or other chemically modified β-cyclodextrins decreased the Pgp binding affinity of 15D3 mAb. UIC2 mAb, which is known to distinguish two conformers of this ABC transporter, binds only a fraction of cell surface Pgps. UIC2 mAb non-reactive pools of Pgp can be identified with other extracellular mAbs such as 15D3. Cyclosporin A (CsA) can shift non-reactive Pgps into their UIC2-reactive conformation: a phenomenon called the "UIC2 shift". Competition studies proposed these two mAbs share overlapping epitopes and can reveal conformational changes of Pgp that correlate (r = 0.97) with the cholesterol content of cells. An apparent increase in competition of these mAbs suggested a conformational change similar to those found in the presence of CsA. However, the reason turned out not to be the UIC2-shift because cholesterol removal from the plasma membrane (PM) reduced the amount of detectable Pgps by 15D3 mAb. This study showed that 15D3 mAb bound to a conformation sensitive epitope of Pgp that was responsive to PM cholesterol levels. These conformational changes were gradual and not as great as the changes observed between the two conformers recognized by the UIC2 mAb. © 2015 Elsevier B.V. All Rights Reserved. Source
Borbas E.,Budapest University of Technology and Economics |
Balogh A.,Budapest University of Technology and Economics |
Bocz K.,Budapest University of Technology and Economics |
Muller J.,Budapest University of Technology and Economics |
And 9 more authors.
International Journal of Pharmaceutics | Year: 2015
Abstract Since it is a well-known fact that among the newly discovered active pharmaceutical ingredients the number of poorly water soluble candidates is continually increasing, dissolution enhancement of poorly water soluble drugs has become one of the central challenges of pharmaceutical studies. So far the preclinical studies have been mainly focused on formulation methods to enhance the dissolution of active compounds, in many cases disregarding the fact that the formulation matrix not only affects dissolution but also has an effect on the transport through biological membranes, changing permeation of the drug molecules. The aim of this study was to test an electrospun cyclodextrin-based formulation of aripiprazole with the novel μFlux apparatus, which monitors permeation together with dissolution, and by this means better in vitro-in vivo correlation is achieved. It was evinced that a cyclodextrin-based electrospun formulation of aripiprazole has the potential to ensure fast drug delivery through the oral mucosa owing to the ultrafast dissolution of the drug from the formulation and the enhanced flux across membranes as shown by the result of the novel in vitro dissolution and permeation test. © 2015 Elsevier B.V. Source
Varga G.,ChiroQuest Chiral Technologies Development Ltd. |
Tarkanyi G.,Hungarian Academy of Sciences |
Nemeth K.,Hungarian Academy of Sciences |
Ivanyi R.,Development Laboratory Ltd. |
And 6 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2010
Preparation of (6-monoureido-6-monodeoxy) permethylated β-cyclodextrin bonded chiral stationary phase from permethylated 6-monoamino-6-monodeoxy-β-cyclodextrin is described. The optimized chiral stationary phase was evaluated by using HPLC separation of racemates of coumarin derivatives. Column characterization was performed by solid-state 13C, 15N, 29Si NMR using cross-polarization at the magic angle spinning. The development process was supported by CE experiments where the complex formation between cyclodextrins and warfarin was investigated. The results demonstrate good enantio-discrimination for coumarin derivatives. © 2009 Elsevier B.V. All rights reserved. Source