Structure and phase behavior of lipid suspensions containing phospholipids with covalently attached poly(ethylene glycol)

Abstract

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.

Cationic Liposomes Coated with Polyethylene Glycol As Carriers for Oligonucleotides

“…Modification of cationic liposomes with PEG-PE allowed the formation of ODN complexes that are stable in size over prolonged storage (Table II). The stabilizing effect of PEG coating on the cationic liposome-ODN complex is likely to result from preventing cross-linking (and thus aggregation and precipitation) of the vesicles by ODN molecules whose stretched length approximates the extension length of the liposome PEG coating in "brush" regime (5-7 nm at Ն 4 mol% PEG-PE) (22,23), as well as avoiding bilayer contact needed for the aggregation to occur. Stabilization of cationic liposomes by PEG coating also contributed to high ODN-binding capacity by allowing the complex to pass through the charge neutralization point at increasing ODN/lipid ratio without aggregation.…”

Flexible membranes with anchored polymers

“…Such lipid anchors have been realized artificially, e.g. for poly(oxyethylene) also known as polyethylene glycol (PEG) [11][12][13], These anchors are also used in biological systems, for example in order to attach cell adhesion molecules (such as N-CAM 120) to cell membranes [9,10]. For such anchors, the whole polymer chain is located on one side of the membrane.…”

Influence of preparation path on the formation of discs and threadlike micelles in DSPE-PEG2000/lipid systems

“…Their presence, however, may seriously influence the aggregate structure. High concentrations of PEG-lipids will, in most phospholipid/PEG-lipid mixtures, induce the formation of mixed spherical micelles [4][5][6][7][8][9][10][11]. Previous studies have shown that two fundamentally different types of mixed micellar aggregates may form at intermediate PEG-lipid to lipid ratios.…”