| 1. |
- Hedge, Oliver, 1991-, et al.
(författare)
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Investigation of Self-Emulsifying Drug-Delivery System Interaction with a Biomimetic Membrane under Conditions Relevant to the Small Intestine
- 2021
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 37:33, s. 10200-10213
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Tidskriftsartikel (refereegranskat)abstract
- Self-emulsifying drug-delivery systems (SEDDS) have been extensively shown to increase oral absorption of solvation-limited compounds. However, there has been little clinical and commercial use of these formulations, in large part because the demonstrated advantages of SEDDS have been outweighed by our inability to precisely predict drug absorption from SEDDS using current in vitro assays. To overcome this limitation and increase the biological relevancy of in vitro assays, an absorption function can be incorporated using biomimetic membranes. However, the effects that SEDDS have on the integrity of a biomimetic membrane are not known. In this study, a quartz crystal microbalance with dissipation monitoring and total internal reflection fluorescence microscopy were employed as complementary methods to in vitro lipolysis-permeation assays to characterize the interaction of various actively digested SEDDS with a liquescent artificial membrane comprising lecithin in dodecane (LiDo). Observations from surface analysis showed that interactions between the digesting SEDDS and LiDo membrane coincided with inflection points in the digestion profiles. Importantly, no indications of membrane damage could be observed, which was supported by flux profiles of the lipophilic model drug felodipine (FEL) and impermeable marker Lucifer yellow on the basal side of the membrane. There was a correlation between the digestion kinetics of the SEDDS and the flux of FEL, but no clear correlation between solubilization and absorption profiles. Membrane interactions were dependent on the composition of lipids within each SEDDS, with the more digestible lipids leading to more pronounced interactions, but in all cases, the integrity of the membrane was maintained. These insights demonstrate that LiDo membranes are compatible with in vitro lipolysis assays for improving predictions of drug absorption from lipid-based formulations.
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| 2. |
- Joyce, Paul, 1989, et al.
(författare)
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TIRF Microscopy-Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica
- 2021
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:4, s. 2069-2073
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biologically active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a ≈500 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small-molecule model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behaviour of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8-facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system-induced changes to cellular membrane permeation.
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| 3. |
- Olsén, Erik, 1994, et al.
(författare)
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Diffusion of Lipid Nanovesicles Bound to a Lipid Membrane Is Associated with the Partial-Slip Boundary Condition
- 2021
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 21:19, s. 8503-8509
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Tidskriftsartikel (refereegranskat)abstract
- During diffusion of nanoparticles bound to a cellular membrane by ligand-receptor pairs, the distance to the laterally mobile interface is sufficiently short for their motion to depend not only on the membrane-mediated diffusivity of the tethers but also in a not yet fully understood manner on nanoparticle size and interfacial hydrodynamics. By quantifying diffusivity, velocity, and size of individual membrane-bound liposomes subjected to a hydrodynamic shear flow, we have successfully separated the diffusivity contributions from particle size and number of tethers. The obtained diffusion-size relations for synthetic and extracellular lipid vesicles are not well-described by the conventional no-slip boundary condition, suggesting partial slip as well as a significant diffusivity dependence on the distance to the lipid bilayer. These insights, extending the understanding of diffusion of biological nanoparticles at lipid bilayers, are of relevance for processes such as cellular uptake of viruses and lipid nanoparticles or labeling of cell-membrane-residing molecules.
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