TY - JOUR
T1 - Exploring the interactions of irbesartan and irbesartan–2-hydroxypropyl-β-cyclodextrin complex with model membranes
AU - Liossi, Adamantia S.
AU - Ntountaniotis, Dimitrios
AU - Kellici, Tahsin F.
AU - Chatziathanasiadou, Maria V.
AU - Megariotis, Grigorios
AU - Mania, Maria
AU - Becker-Baldus, Johanna
AU - Kriechbaum, Manfred
AU - Krajnc, Andraž
AU - Christodoulou, Eirini
AU - Glaubitz, Clemens
AU - Rappolt, Michael
AU - Amenitsch, Heinz
AU - Mali, Gregor
AU - Theodorou, Doros N.
AU - Valsami, Georgia
AU - Pitsikalis, Marinos
AU - Iatrou, Hermis
AU - Tzakos, Andreas G.
AU - Mavromoustakos, Thomas
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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 1 nm from the membrane centre.
AB - 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 1 nm from the membrane centre.
KW - DPPC
KW - HP-β-CD
KW - Irbesartan
KW - Molecular dynamics
KW - Small angle X-ray scattering
UR - http://www.scopus.com/inward/record.url?scp=85015432378&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2017.03.003
DO - 10.1016/j.bbamem.2017.03.003
M3 - Article
C2 - 28274845
AN - SCOPUS:85015432378
SN - 0005-2736
VL - 1859
SP - 1089
EP - 1098
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 6
ER -