Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Localization of the ibuprofen molecule in model lipid membranes revealed by spin-label-enhanced NMR relaxation. / Kashnik, Anna S; Selyutina, Olga Yu; Baranov, Denis S и др.
в: Biochimica et Biophysica Acta - Biomembranes, Том 1865, № 8, 184215, 12.2023.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
}
TY - JOUR
T1 - Localization of the ibuprofen molecule in model lipid membranes revealed by spin-label-enhanced NMR relaxation
AU - Kashnik, Anna S
AU - Selyutina, Olga Yu
AU - Baranov, Denis S
AU - Polyakov, Nikolay E
AU - Dzuba, Sergei A
N1 - This work was supported by the Russian Science Foundation, project # 21-13-00025. Copyright © 2023 Elsevier B.V. All rights reserved.
PY - 2023/12
Y1 - 2023/12
N2 - Non-steroidal anti-inflammatory drugs (NSAIDs) have antipyretic, anti-inflammatory and analgesic effects, and can be used in the treatment of various diseases. These drugs have also a number of side effects, which may be related to their interaction with lipid membranes. In this study, we use the spin-labeled NSAID ibuprofen (ibuprofen-SL) as a relaxation enhancer to study its interaction with model lipid membranes employing liquid-state 1H NMR at 500 MHz. The high magnetic moment of unpaired electron in the spin label made it possible to reduce the concentration of the studied drug in the membrane to tenths of a mole percent. As model membranes, unilamellar POPC liposomes and bicelles consisting of a 2:1 mixture of DHPC:DMPC or DHPC:POPC lipids were used. An increase in the rate of proton spin-lattice relaxation, T1-1, selectively detected for protons at different positions in the lipid molecule, showed that ibuprofen-SL is localized in the hydrophobic part of the lipid bilayer. As the concentration of ibuprofen-SL increases to 0.5 mol%, the distribution of positions of ibuprofen-SL across the bilayer becomes wider. In the presence of 20 mol% of cholesterol, ibuprofen-SL is displaced from the core of the membrane to a region closer to the head group of the bilayer. This displacement was also confirmed by the NMR NOESY experiment conducted with unlabeled ibuprofen. For bilayers containing unsaturated POPC lipids, the distribution of ibuprofen positions across the bilayer becomes narrower compared to the presence of saturated DMPC lipids.
AB - Non-steroidal anti-inflammatory drugs (NSAIDs) have antipyretic, anti-inflammatory and analgesic effects, and can be used in the treatment of various diseases. These drugs have also a number of side effects, which may be related to their interaction with lipid membranes. In this study, we use the spin-labeled NSAID ibuprofen (ibuprofen-SL) as a relaxation enhancer to study its interaction with model lipid membranes employing liquid-state 1H NMR at 500 MHz. The high magnetic moment of unpaired electron in the spin label made it possible to reduce the concentration of the studied drug in the membrane to tenths of a mole percent. As model membranes, unilamellar POPC liposomes and bicelles consisting of a 2:1 mixture of DHPC:DMPC or DHPC:POPC lipids were used. An increase in the rate of proton spin-lattice relaxation, T1-1, selectively detected for protons at different positions in the lipid molecule, showed that ibuprofen-SL is localized in the hydrophobic part of the lipid bilayer. As the concentration of ibuprofen-SL increases to 0.5 mol%, the distribution of positions of ibuprofen-SL across the bilayer becomes wider. In the presence of 20 mol% of cholesterol, ibuprofen-SL is displaced from the core of the membrane to a region closer to the head group of the bilayer. This displacement was also confirmed by the NMR NOESY experiment conducted with unlabeled ibuprofen. For bilayers containing unsaturated POPC lipids, the distribution of ibuprofen positions across the bilayer becomes narrower compared to the presence of saturated DMPC lipids.
KW - Ibuprofen
KW - Dimyristoylphosphatidylcholine
KW - Anti-Inflammatory Agents, Non-Steroidal
KW - Electrons
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85169015108&origin=inward&txGid=1706ef14f4b140940ba8cf2aa915b28d
U2 - 10.1016/j.bbamem.2023.184215
DO - 10.1016/j.bbamem.2023.184215
M3 - Article
C2 - 37633627
VL - 1865
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 8
M1 - 184215
ER -
ID: 55287210