| 1. |
- Edwards, Katarina, et al.
(författare)
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Effect of polyethyleneglycol-phospholipids on aggregate structure in preparations of small unilamellar liposomes
- 1997
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Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 73:1, s. 258-266
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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.
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| 2. |
- Silvander, M., et al.
(författare)
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Rheological properties of phospholipid-stabilized parenteral oil-in-water emulsions - effects of electrolyte concentration and presence of heparin
- 2003
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 252:02-jan, s. 123-132
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Tidskriftsartikel (refereegranskat)abstract
- The rheological properties of the parenteral oil-in-water emulsion Intralipid(TM) were investigated. The viscosity data at different phase volumes correlated well with that obtained via a theoretical model developed by Yaron and Gal-Or. The model also describes the temperature dependence well. The effects of electrolyte addition were also investigated. Monovalent sodium chloride had practically no influence on viscosity. Calcium chloride, on the other hand, had a large impact on viscosity even at low concentrations. It was shown that the obtained maximum in viscosity coincided with the zeta-potential being close to zero. The resulting increase in viscosity is due to flocculation that leads to an increase in apparent phase volume. A similar behaviour was obtained with magnesium chloride with the difference that the maximum in viscosity was shifted to higher electrolyte concentrations. This is interpreted as that because magnesium binds strongly to the hydration water than does calcium. The addition of the negatively charged anti-coagulant heparin causes flocculation in the presence of small amounts of calcium. The amounts of calcium needed for such bridging flocculation is lower than what is needed in order to create a positive potential at the surfaces of the droplets. A fraction of the floes is not broken down even by extensive shear.
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| 8. |
- Silvander, M, et al.
(författare)
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Linkage identity is a major factor in determining the effect of PEG-ylated surfactants on permeability of phosphatidylcholine liposomes
- 2003
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Ingår i: Chemistry and Physics of Lipids. - 0009-3084 .- 1873-2941. ; 126, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- The permeability effects induced by single-chained and double-chained poly(ethylene glycol)-surfactants were investigated by measuring the leakage of the fluorescent dye 5(6)-carboxy fluorescein from EPC liposomes. The standard incorporated amount of the surfactants was 5 mol%. Depending on the size of the poly(ethylene glycol) chain and especially on the type of linkage between the polymer and the hydrophobic moiety different leakage profiles were obtained. The presence of a long PEG-polymer resulted in a slower leakage compared with a short analogue. More importantly, the linkage identity was decisive for whether an overall reduction or increase in permeability was obtained. When the hydrocarbon chains were attached to the PEG chain via an ether or an ester the leakage increased compared to pure EPC liposomes. In contrast, if the link was an amide, the leakage was significantly reduced. This effect is assumed to originate from headgroup–headgroup interactions, and most probably hydrogen bonding, between amide and phosphate groups of the PEG-surfactant and the EPC, respectively
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| 9. |
- Silvander, M, et al.
(författare)
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Liposomal surface potential and bilayer packing as affected by PEG-lipid inclusion
- 2000
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Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 16, s. 3696-3702
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Tidskriftsartikel (refereegranskat)abstract
- The surface potentials and the packing properties of phospholipid liposomes containing anionic lipids with covalently attached poly(ethylene glycol) polymers (PEG(2000)-PE) were investigated. The negative surface potential induced by the PEG-lipid in EPC/cholesterol and SPC/cholesterol liposomes was determined by means of titration of the fluorescent probe 4-heptadecyl-7-hydroxycoumarin (HC). The shift in the apparent pK of the probe corresponds to an induced potential of -13 mV for 5 mol % PEG-lipid in the phospholipid/cholesterol (ionic strength = 150 mM). For EPC liposomes without cholesterol, 5 mol % PEG-lipid did not cause any detectable shift in the pK of the probe. This indicates that the EPC liposome surface in fact carries a net negative charge. The above results were supported by determinations of the potential. The packing order of the outer and inner parts of the phospholipid/cholesterol bilayer membranes was investigated by fluorescence depolarization anisotropy of the probes HC and 1,6-diphenyl-1,3,5-hexatriene (DPH). The PEG-lipid inclusion caused an increase in the anisotropy of HC, located at the water/hydrocarbon interface. In addition, a small increase in anisotropy was observed for DPH upon PEG-lipid inclusion. Since DPH is situated in the hydrocarbon region, these data together with the HC data indicate that the PEG-lipids impose restrictions on the molecular motion in the outer as well as the inner parts of the hydrocarbon region.
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| 10. |
- Silvander, M, et al.
(författare)
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Liposomal surface potential and bilayer packing as affected by PEG-lipid inclusion
- 2000
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Ingår i: LANGMUIR. - : AMER CHEMICAL SOC. - 0743-7463. ; 16:8, s. 3696-3702 Language: English
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Tidskriftsartikel (refereegranskat)abstract
- The surface potentials and the,packing properties of phospholipid Liposomes containing anionic lipids with covalently attached poly(ethylene glycol) polymers (PEG(2000)-PE) were investigated. The negative surface potential induced by the PEG-lipid in EPC/
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