| 1. |
- Forooqi Motlaq, Vahid, et al.
(författare)
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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
- 2022
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier. - 0005-2736 .- 1879-2642. ; 1864:10
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Forooqi Motlaq, Vahid, et al.
(författare)
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Investigation of the enhanced ability of bile salt surfactants to solubilize phospholipid bilayers and form mixed micelles.
- 2021
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Ingår i: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 17:33, s. 7769-7780
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Tidskriftsartikel (refereegranskat)abstract
- The self-assembly in mixtures of the anionic bile salt surfactant sodium deoxycholate (NaDC) and the zwitterionic phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in physiological saline solution has been investigated using light scattering, small-angle X-ray scattering and cryo-transmission electron microscopy. Rather small tri-axial ellipsoidal NaDC-DMPC mixed micelles form at a high content of bile salt in the mixture, which increase in size as an increasing amount of DMPC is incorporated into the micelles. Eventually, the micelles begin to grow substantially in length to form long wormlike micelles. At higher mole fractions of DMPC, the samples become turbid and cryo-TEM measurements reveal the existence of large perforated vesicles (stomatosomes), coexisting with geometrically open disks. To our knowledge, stomatosomes have not been observed before for any bile salt-phospholipid system. Mixed micelles are found to be the sole aggregate structure in a very wide regime of bile salt-phospholipid compositions, i.e. up to about 77 mol% phospholipid in the micelles. This is much higher than the corresponding value of 25 mol% observed for the conventional surfactant hexadecyltrimethylammonium bromide (CTAB) mixed with DMPC in the same solvent. The enhanced ability of bile salt surfactants to solubilize phospholipid bilayers and form mixed micelles is rationalized using bending elasticity theory. From our theoretical analysis, we are able to conclude that amphiphilic molecules rank in the following order of increasing spontaneous curvature: phospholipids < conventional surfactants < bile salts. The bending rigidity of the different amphiphilic molecules increases according to the following sequence: bile salts < conventional surfactants < phospholipids.
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| 3. |
- Forooqi Motlaq, Vahid, et al.
(författare)
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Spontaneous Formation of Ultrasmall Unilamellar Vesicles in Mixtures of an Amphiphilic Drug and a Phospholipid
- 2023
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 39:32, s. 11337-11344
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Tidskriftsartikel (refereegranskat)abstract
- We have observed ultrasmall unilamellar vesicles, withdiametersof less than 20 nm, in mixtures of the tricyclic antidepressant drugamitriptyline hydrochloride (AMT) and the unsaturated zwitterionicphospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in physiologicalsaline solution. The size and shape of spontaneously formed self-assembledaggregates have been characterized using complementary techniques,i.e., small-angle neutron and X-ray scattering (SANS and SAXS) andcryo-transmission electron microscopy (cryo-TEM). We observe rodlikemixed micelles in more concentrated samples that grow considerablyin length upon dilution, and a transition from micelles to vesiclesis observed as the concentration approaches the critical micelle concentrationof AMT. Unlike the micelles, the spontaneously formed vesicles decreasein size with each step of dilution, and ultrasmall unilamellar vesicles,with diameters as small as about 15 nm, were observed at the lowestconcentrations. The spontaneously formed ultrasmall unilamellar vesiclesmaintain their size for as long we have investigated them (i.e., severalmonths). To the best of our knowledge, such small vesicles have neverbefore been reported to form spontaneously in a biocompatible phospholipid-basedsystem. Most interestingly, the size of the vesicles was observedto be strongly dependent on the chemical structure of the phospholipid,and in mixtures of AMT and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC), the vesicles were observed to be considerably larger in size.The self-assembly behavior in the phospholipid-drug surfactantsystem in many ways resembles the formation of equilibrium micellesand vesicles in mixed anionic/cationic surfactant systems.
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