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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 28 (1989), S. 7700-7707 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 1775-1780 
    ISSN: 1573-904X
    Keywords: liposomes ; drug delivery ; GM1 ; opsonin ; liver perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. We have previously reported that GMl exhibits an opposite effect on regulating liposome circulation time in mice and rats (Liu et al. Pharm. Res. Vol. 12:508-512 (1995)). Inclusion of GM1 into liposomes significantly prolongs liposome circulation time in mice, while it dramatically decreases the blood half life and increases liver uptake of liposomes in rats. The purpose of this study was to elucidate the mechanism that underlies this phenomenon. Methods. Single-pass liver perfusion in vitro and complement mediated liposome lysis assay was used. Results. Serum appeared to play an important role in determining the liver uptake of GMl liposomes. Specifically, rat serum enhanced the uptake of GM1 containing liposomes by the perfused liver. Such activity was also found in human and bovine serum, but not in mouse serum. Taking human serum as an example, we demonstrated that such serum activity can be blocked by EDTA and EGTA/Mg2 +. Antibodies against human IgM and the third component of complement system (C3) also inhibited serum activity. Conclusions. The presence of naturally occurring anti-GM1 antibodies in rats, through the activation of the classic pathway of complement system, is likely the cause of rapid blood clearance of GM1 liposomes. The third component of complement is likely to serve as the opsonin that is directly involved in mediating liposome clearance.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 508-512 
    ISSN: 1573-904X
    Keywords: drug delivery ; ganglioside GM1 ; liposomes ; opsonin ; reticuloendothelial system ; complement system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Inclusion of monosialoganglioside GM1 into liposomes significantly enhances the circulation time of liposomes in mice. Conversely, intravenously injected GM1-containing liposomes were rapidly removed from the blood circulation and accumulated in the liver and spleen in rats. In rats, increasing the GM1 content in liposomes resulted in more rapid clearance from the blood. Increasing the membrane rigidity of liposomes further increased the liver uptake of GM1-containing liposomes. The activity of GM1 in enhancing the liposome uptake by rat liver appears to be mediated by complement components.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 13 (1996), S. 1856-1860 
    ISSN: 1573-904X
    Keywords: gene transfer ; gene therapy ; cationic lipid ; transfection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop appropriate dosage forms of DNA for gene delivery. Methods. 3β[N-(N′, N′ dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) was mixed either with Tween 80 alone, or with additional lipid components including castor oil and phosphatidylcholine (PC) or dioleoylphosphatidylethanolamine (DOPE) to make different lipid formulations. The particle size and the physical stability of the formulations upon mixing with plasmid DNA containing the luciferase cDNA were examined using laser light scattering measurement. The transfection activity of the DNA/lipid complexes was tested in presence or absence of serum using a cell culture system. Results. We demonstrated that many favorable properties as a gene carrier could be achieved by formulating DNA into new dosage forms using Tween 80 as the major emulsifier. Compared to the cationic liposomes, these new formulations transfected different cell lines with an equivalent or higher efficiency. Not only are they resistant to serum, but also form stable DNA complexes which could be stored for longer periods of time without losing transfection activity. Conclusions. Cationic lipids formulated into different lipid formulations using Tween 80 as a surfactant appeared to have more favorable physical and biological activities than traditional cationic liposomes as a carrier for gene delivery.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-904X
    Keywords: emulsions ; gene transfer ; transfection ; gene therapy ; non-ionic surfactant ; cationic lipid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the structure-function relationship of non-ionic surfactants in emulsion-mediated gene delivery. Methods. Four different types of non-ionic surfactants including Tween, Span, Brij and pluronic copolymers were used as co-emulsifiers for preparation of emulsions composed of Castor oil, dioleoylphosphatidylethanolamine (DOPE) and 3β[N-(N′, N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol). The effect of different surfactants on the formation of DNA/emulsion complexes and transfection activity were analyzed using plasmid DNA containing luciferase cDNA as a reporter gene. Results. Non-ionic surfactants containing branched polyoxyethylene chains as the hydrophilic head group were more effective in preventing the formation of large DNA/emulsion complexes than those containing one or no polyoxyethylene chain. All emulsion formulations except those containing Brij 700 exhibited high activity in transfecting mouse BL-6 cells in the absence of serum. In the presence of serum, however, transfection activity of each formulation varied significantly. Emulsions containing Tween, Brij 72, pluronic F68 and F127 demonstrated increased activity in transfecting cells in the presence of 20% serum. In contrast to emulsions containing Span, long chain polyoxyethylene of Brij showed decreased transfection activity. The particle size of the DNA/emulsion complexes and their ability to transfect cells are dependent on the concentration of non-ionic surfactant in the formulation. Conclusions. The structure of the hydrophilic head group of the non-ionic surfactants in the emulsion is important in determining how DNA molecules interact with emulsions and the extent to which DNA is transferred inside the cell.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 1060-1064 
    ISSN: 1573-904X
    Keywords: long-circulating emulsions ; polyethyleneglycol ; reticuloendothelial system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Rapid clearance of parenterally administered oil-in-water emulsions from blood by the reticuloendothelial system (RES), mainly macrophages of the liver and spleen, has been one of the major obstacles for delivering lipophilic drugs to cells other than those in the RES. The purpose of this study therefore is to overcome this problem and develop emulsions that will have prolonged blood circulation time. Methods. A series of amphipathic polyethylene-glycol (PEG) derivatives have been included as co-emulsifier into emulsions composed of Castor oil and phosphatidylcholine. The effect of amphipathic PEG on reducing the RES uptake and prolonging the blood circulation of the emulsion particles has been tested in vivo using mice as an animal model. Results. Inclusion of PEG derivatives such as Tween-80 or dioleoyl N-(monomethoxy-polyethyleneglycol succinyl)phosphotidylethanolamine (PEG-PE) into emulsions composed of Castor oil and phosphatidylcholine decreases the RES uptake and increases blood residence time of the emulsions. The activity of PEG derivatives in prolonging the circulation time of emulsions depends on the PEG chain length (PEG2000≥PEG5000〉PEG1000, Tween-80) and the PEG density on emulsion surface. Conclusions. Inclusion of amphipathic PEG as emulsifier into oil-in-water emulsions is a very effective method to prolong the blood half life of the emulsions. Emulsions with long circulating half life in blood should be very useful as a delivery vehicle for lipophilic drugs.
    Type of Medium: Electronic Resource
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