Development and initial evaluation of PEG-stabilized bilayer disks as novel model membranes.
We show in this study that stable dispersions dominated by flat bilayer disks may be prepared from a carefully optimized mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-5000] [PEG-DSPE(5000)]. By varying the content of the latter component, the average diameter of the disks can be changed in the interval from about 15 to 60 nm. The disks show excellent long-term stability, and their size and structure remain unaltered in the temperature range between 25 and 37 degrees C. The utility of the disks as artificial model membranes was confirmed and compared to uni- and multilamellar liposomes in a series of drug partition studies. Data obtained by isothermal titration calorimetry and drug partition chromatography (also referred to as immobilized liposome chromatography) indicate that the bilayer disks may serve as an attractive and sometimes superior alternative to liposomes in studies aiming at the investigation of drug-membrane interactions. The disks may, in addition, hold great potential for structure/function studies of membrane-bound proteins. Furthermore, we suggest that the sterically stabilized bilayer disks may prove interesting as carriers for in vivo delivery of protein/peptide, as well as conventional amphiphilic and/or hydrophobic, drugs.
Johansson
Emma
E
Department of Physical Chemistry, Biomedical Center, Uppsala University, Box 579, SE-75123 Uppsala, Sweden.
Engvall
Caroline
C
Arfvidsson
Maria
M
Lundahl
Per
P
Edwards
Katarina
K
D002784:Cholesterol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008566:Membranes; D008954:Models, Biological; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D013499:Surface Properties
D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011506:Proteins; D011092:Polyethylene Glycols; D002784:Cholesterol; C010942:1,2-distearoyllecithin