Exploring the interactions of irbesartan and irbesartan-2-hydroxypropyl-β-cyclodextrin complex with model membranes

Αdamantia S Liossi; Dimitrios Ntountaniotis; Tahsin F Kellici; Maria V Chatziathanasiadou; Grigorios Megariotis; Maria Mania; Johanna Becker-Baldus; Manfred Kriechbaum; Andraž Krajnc; Eirini Christodoulou; Clemens Glaubitz; Michael Rappolt; Heinz Amenitsch; Gregor Mali; Doros N Theodorou; Georgia Valsami; Marinos Pitsikalis; Hermis Iatrou; Andreas G Tzakos; Thomas Mavromoustakos

doi:10.1016/j.bbamem.2017.03.003

Exploring the interactions of irbesartan and irbesartan-2-hydroxypropyl-β-cyclodextrin complex with model membranes

Biochim Biophys Acta Biomembr. 2017 Jun;1859(6):1089-1098. doi: 10.1016/j.bbamem.2017.03.003. Epub 2017 Mar 6.

Authors

Αdamantia S Liossi¹, Dimitrios Ntountaniotis¹, Tahsin F Kellici², Maria V Chatziathanasiadou³, Grigorios Megariotis⁴, Maria Mania⁵, Johanna Becker-Baldus⁶, Manfred Kriechbaum⁷, Andraž Krajnc⁸, Eirini Christodoulou⁹, Clemens Glaubitz⁶, Michael Rappolt¹⁰, Heinz Amenitsch⁷, Gregor Mali⁸, Doros N Theodorou⁴, Georgia Valsami⁹, Marinos Pitsikalis¹, Hermis Iatrou¹, Andreas G Tzakos³, Thomas Mavromoustakos¹¹

Affiliations

¹ Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
² Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece; Department of Chemistry, University of Ioannina, GR-45110, Greece.
³ Department of Chemistry, University of Ioannina, GR-45110, Greece.
⁴ School of Chemical Engineering, National Technical University of Athens, Athens, Greece.
⁵ Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece; Department of Chemistry, University of Patras, Rio 26510, Greece.
⁶ Institute of Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
⁷ Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9/5, A-8010 Graz, Austria.
⁸ National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
⁹ Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
¹⁰ School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK.
¹¹ Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece; Department of Chemistry, York College and the Graduate Center of the City University of New York, 94-20 Guy R. Brewer Blvd., Jamaica, New York, 11451, United States. Electronic address: tmavrom@chem.uoa.gr.

PMID: 28274845
DOI: 10.1016/j.bbamem.2017.03.003

Abstract

The interactions of irbesartan (IRB) and irbesartan-2-hydroxypropyl-β-cyclodextrin (HP-β-CD) complex with dipalmitoyl phosphatidylcholine (DPPC) bilayers have been explored utilizing an array of biophysical techniques ranging from differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), ESI mass spectrometry (ESI-MS) and solid state nuclear magnetic resonance (ssNMR). Molecular dynamics (MD) calculations have been also conducted to complement the experimental results. Irbesartan was found to be embedded in the lipid membrane core and to affect the phase transition properties of the DPPC bilayers. SAXS studies revealed that irbesartan alone does not display perfect solvation since some coexisting irbesartan crystallites are present. In its complexed form IRB gets fully solvated in the membranes showing that encapsulation of IRB in HP-β-CD may have beneficial effects in the ADME properties of this drug. MD experiments revealed the topological and orientational integration of irbesartan into the phospholipid bilayer being placed at about 1nm from the membrane centre.

Keywords: DPPC; HP-β-CD; Irbesartan; Molecular dynamics; Small angle X-ray scattering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1,2-Dipalmitoylphosphatidylcholine / chemistry*
2-Hydroxypropyl-beta-cyclodextrin
Antihypertensive Agents / chemistry*
Biphenyl Compounds / chemistry*
Drug Compounding
Freeze Drying
Irbesartan
Kinetics
Lipid Bilayers / chemistry*
Liposomes / chemistry*
Molecular Dynamics Simulation
Phase Transition
Tetrazoles / chemistry*
Thermodynamics
beta-Cyclodextrins / chemistry*

Substances

Antihypertensive Agents
Biphenyl Compounds
Lipid Bilayers
Liposomes
Tetrazoles
beta-Cyclodextrins
2-Hydroxypropyl-beta-cyclodextrin
1,2-Dipalmitoylphosphatidylcholine
Irbesartan