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Dissolution mechanism of supported phospholipid bilayer in the presence of amphiphilic drug investigated by neutron reflectometry and quartz crystal microbalance with dissipation monitoring
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- Forooqi Motlaq, Vahid (author)
- Uppsala universitet,Institutionen för läkemedelskemi,Institutionen för farmaci
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- Adlmann, Franz A. (author)
- Uppsala universitet,Institutionen för farmaci,Institutionen för läkemedelskemi
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- Agmo Hernández, Víctor (author)
- Uppsala universitet,Institutionen för läkemedelskemi
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- (creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
- In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier. - 0005-2736 .- 1879-2642. ; 1864:10
- Journal article (peer-reviewed)
Abstract
Subject headings
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- The influence and interaction of the ionizable amphiphilic drug amitriptyline hydrochloride (AMT) on a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid bilayer supported on a silica surface have been investigated using a combination of neutron reflectometry and quartz crystal microbalance with dissipation monitoring. Adding AMT solutions with concentrations 3, 12, and 50 mM leaves the lipid bilayer mainly intact and we observe most of the AMT molecules attached to the head-group region of the outer bilayer leaflet. Virtually no AMT penetrates into the hydrophilic head-group region of the inner leaflet close to the silica surface. By adding 200 mM AMT solution, the lipid bilayer dissolved entirely, indicating a threshold concentration for the solubilization of the bilayer by AMT. The observed threshold concentration is consistent with the observation that various bilayer structures abruptly transform into mixed AMT-DOPC micelles beyond a certain AMT-DOPC composition. Based on our experimental observations, we suggest that the penetration of drug into the phospholipid bilayer, and subsequent solubilization of the membrane, follows a two-step mechanism with the outer leaflet being removed prior to the inner leaflet.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Lipid bilayer
- Phospholipid
- DOPC
- Amitriptyline
- Neutron reflectometry
- Amphiphilic drug
- Membrane transport
- Membrane solubilization
- SLB
Publication and Content Type
- ref (subject category)
- art (subject category)
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