title: Optimization of lipodisk properties by modification of the extent and density of the PEG corona.
abstract: Lipodisks are nanosized flat, circular, phospholipid bilayers that are edge-stabilized by polyethylene glycol-conjugated lipids (PEG-lipids). Over the last decade, lipodisks stabilized with PEG of molecular weight 2000 or 5000 have been shown to hold high potential as both biomimetic membranes and drug carriers. In this study we investigate the possibilities to optimize the properties of the lipodisks, and widen their applicability, by reducing the PEG molecular weight and/or the density of the PEG corona. Results obtained by cryo-transmission electron microscopy and dynamic light scattering show that stable, well-defined lipodisks can be produced from mixtures of distearoylphosphatidylcholine (DSPC) and distearoylphosphatidylethanolamine conjugated to PEG of molecular weight 1000 (DSPE-PEG1000). Preparations based on the use of DSPE-PEG750tend, in contrast, to be polydisperse in size and structure. By comparing immobilization of lipodisks stabilized with DSPE-PEG1000, DSPE-PEG2000,and DSPE-PEG5000to porous and smooth silica surfaces, we show that the amount of surface bound disks can be considerably improved by the use of PEG-lipids with reduced molecular weight. Further, a modified preparation protocol that enables production of lipodisks with very low PEG-lipid content is described. The reduced PEG density, which facilitates the incorporation of externally added ligand-linked PEG-lipids, is shown to be beneficial for the production of targeting lipodisks.
authors: Department of Chemistry - BMC, Uppsala University, Box 579, SE-752 37 Uppsala, Sweden. Electronic address: malin.zetterberg@kemi.uu.se.
authors: Malin Morin
authors: MM
authors: Zetterberg
authors: Department of Chemistry - BMC, Uppsala University, Box 579, SE-752 37 Uppsala, Sweden. Electronic address: sara.ahlgren@kemi.uu.se.
authors: Sara
authors: S
authors: Ahlgren
authors: Department of Chemistry - BMC, Uppsala University, Box 579, SE-752 37 Uppsala, Sweden. Electronic address: victor.agmo@kemi.uu.se.
authors: Víctor
authors: V
authors: Agmo Hernández
authors: Department of Physics, Biological Physics Division, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden. Electronic address: nagma.parveen@chalmers.se.
authors: Nagma
authors: N
authors: Parveen
authors: Department of Chemistry - BMC, Uppsala University, Box 579, SE-752 37 Uppsala, Sweden. Electronic address: katarina.edwards@kemi.uu.se.
authors: Katarina
authors: K
authors: Edwards
mesh_terms: D045744:Cell Line, Tumor; D004337:Drug Carriers; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D058990:Molecular Targeted Therapy; D008970:Molecular Weight; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D016062:Porosity; D011485:Protein Binding; D012822:Silicon Dioxide / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004337:Drug Carriers; D007457:Iodine Radioisotopes; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D012822:Silicon Dioxide; C010942:1,2-distearoyllecithin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Bilayer disks; Biomimetic membranes; Drug delivery; Lipid self-assembly; Nanocarriers; Specific targeting; Surface immobilization