title: Exploring the interactions of irbesartan and irbesartan-2-hydroxypropyl-β-cyclodextrin complex with model membranes.
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.
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Αdamantia S
authors.initials: ΑS
authors.lastname: Liossi
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Ntountaniotis
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece; Department of Chemistry, University of Ioannina, GR-45110, Greece.
authors.forename: Tahsin F
authors.initials: TF
authors.lastname: Kellici
authors.affiliation: Department of Chemistry, University of Ioannina, GR-45110, Greece.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Chatziathanasiadou
authors.affiliation: School of Chemical Engineering, National Technical University of Athens, Athens, Greece.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Megariotis
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece; Department of Chemistry, University of Patras, Rio 26510, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Mania
authors.affiliation: Institute of Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Becker-Baldus
authors.affiliation: Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9/5, A-8010 Graz, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kriechbaum
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
authors.forename: Andraž
authors.initials: A
authors.lastname: Krajnc
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Eirini
authors.initials: E
authors.lastname: Christodoulou
authors.affiliation: Institute of Biophysical Chemistry and Centre for Biomolecular Magnetic Resonance, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Glaubitz
authors.affiliation: School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Rappolt
authors.affiliation: Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9/5, A-8010 Graz, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Amenitsch
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Mali
authors.affiliation: School of Chemical Engineering, National Technical University of Athens, Athens, Greece.
authors.forename: Doros N
authors.initials: DN
authors.lastname: Theodorou
authors.affiliation: Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Valsami
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Marinos
authors.initials: M
authors.lastname: Pitsikalis
authors.affiliation: Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece.
authors.forename: Hermis
authors.initials: H
authors.lastname: Iatrou
authors.affiliation: Department of Chemistry, University of Ioannina, GR-45110, Greece.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000959:Antihypertensive Agents / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D004339:Drug Compounding; D005612:Freeze Drying; D000077405:Irbesartan; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D044367:Phase Transition; D013777:Tetrazoles / Q000737:chemistry*; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D008051:Lipid Bilayers; D008081:Liposomes; D013777:Tetrazoles; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015060:1,2-Dipalmitoylphosphatidylcholine; D000077405:Irbesartan
keywords: DPPC; HP-β-CD; Irbesartan; Molecular dynamics; Small angle X-ray scattering