Effect of polyethyleneglycol-phospholipids on aggregate structure in preparations of small unilamellar liposomes

Abstract

Phospholipids with covalently attached poly(ethylene glycol) (PEG lipids) are commonly used for the preparation of long circulating liposomes. Although it is well known that lipid/PEG-lipid mixed micelles may form above a certain critical concentration of PEG-lipid, little is known about the effects of PEG-lipids on liposome structure and leakage at submicellar concentrations. In this study we have used cryogenic transmission electron microscopy to investigate the effect of PEG(2000)-PE on aggregate structure in preparations of liposomes with different membrane compositions. The results reveal a number of important aggregate structures not documented before. The micrographs show that enclosure of PEG-PE induces the formation of open bilayer discs at concentrations well below those where mixed micelles begin to form. The maximum concentration of PEG-lipid that may be incorporated without alteration of the liposome structure depends on the phospholipid chain length, whereas phospholipid saturation or the presence of cholesterol has little or no effect. The presence of cholesterol does, however, affect the shape of the mixed micelles formed at high concentrations of PEG-lipid. Threadlike micelles form in the absence of cholesterol but adapt a globular shape when cholesterol is present.

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.…”

“…Previous studies have shown that two fundamentally different types of mixed micellar aggregates may form at intermediate PEG-lipid to lipid ratios. Depending on the characteristics of the lipid mixture the PEG-lipids induce formation of either long threadlike or discoidal micelles [7,10,12,13]. Threadlike micelles are, for example, commonly observed in PEG-lipid/lipid samples where the lipid is in the liquid crystalline phase, while discs are observed in such mixtures supplemented with cholesterol [7,12].…”

“…Depending on the characteristics of the lipid mixture the PEG-lipids induce formation of either long threadlike or discoidal micelles [7,10,12,13]. Threadlike micelles are, for example, commonly observed in PEG-lipid/lipid samples where the lipid is in the liquid crystalline phase, while discs are observed in such mixtures supplemented with cholesterol [7,12]. Further, discoidal micelles are formed in cases where the lipid is in the gel phase [10,12,13].…”

Effect of chain lengths of PEO–PPO–PEO on small unilamellar liposome morphology and stability: an AFM investigation

“…The transition from vesicles to open structure and to an intermediate domain in which both vesicles and bilayer coexist were also observed and described for phospholipids/cholesterol/PEG-PE [37] and phospholipid/ Pluronic ® systems [11]. The transition mechanism was explained in terms of vesicle-to-micelle transition [37].…”

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

“…Lipid-anchored PEG stabilizes the liposome and prevents the rapid recognition and consequent uptake of MLs via the mononuclear phagocyte system. [23][24][25] In addition, functionalized derivatives of PEG-lipids can be used for the convenient coupling of targeting sequences to the surface of the liposomes to achieve specific cellular recognition. Here, we have synthesized PEG-coated stealth magnetic liposomes (sMLs) by evaluating two different types of commercially available USPIOs.…”