Structure and phase behavior of lipid suspensions containing phospholipids with covalently attached poly(ethylene glycol).
Liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are being developed for in vivo drug delivery. In this paper we determine the structure and phase behavior of fully hydrated distearoylphosphatidylcholine (DSPC) suspensions containing PEG-lipids composed of distearoylphosphatidylethanolamine with attached PEGs of molecular weights ranging from 350 to 5000. For DSPC:PEG-lipid suspensions containing 0-60 mol % PEG-lipid, differential scanning calorimetry shows main endothermic transitions ranging from 55 to 64 degrees C, depending on the size of the PEG and concentration of PEG-lipid. The enthalpy of this main transition remains constant for all PEG-350 concentrations but decreases with increasing amounts of PEG-750, PEG-2000, or PEG-5000, ultimately disappearing at PEG-lipid concentrations greater than about 60 mol %. Low-angle and wide-angle x-ray diffraction show that tilted gel (L beta') phase bilayers are formed for all PEG-lipid molecular weights at concentrations of about 10 mol % or less, with the distance between bilayers depending on PEG molecular weight and PEG-lipid concentration. At PEG-lipid concentrations greater than 10 mol %, the lipid structure depends on the size of the PEG moiety. X-ray diffraction analysis shows that untilted interdigitated (L beta I) gel phase bilayers form with the incorporation of 40-100 mol % PEG-350 or 20-70 mol % PEG-750, and untilted gel (L beta) phase bilayers are formed in the presence of about 20-60 mol % PEG-2000 and PEG-5000. Light microscopy, turbidity measurements, x-ray diffraction, and 1H-NMR indicate that a pure micellar phase forms in the presence of greater than about 60% PEG-750, PEG-2000, or PEG-5000.
Kenworthy
A K
AK
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Simon
S A
SA
McIntosh
T J
TJ
D002152:Calorimetry, Differential Scanning; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008853:Microscopy; D008961:Models, Structural; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000737:chemistry*; D011092:Polyethylene Glycols; D013053:Spectrophotometry; D013535:Suspensions; D013816:Thermodynamics; D014961:X-Ray Diffraction
D008081:Liposomes; D010713:Phosphatidylcholines; D013535:Suspensions; D011092:Polyethylene Glycols; C010942:1,2-distearoyllecithin