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  • 1
    Electronic Resource
    Electronic Resource
    Effects of Polyethyleneglycol Chain Length and Phospholipid Acyl Chain Composition on the Interaction of Polyethyleneglycol-phospholipid Conjugates with Phospholipid: Implications in Liposomal Drug Delivery (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 710-717 
    Details
    ISSN: 1573-904X
    Keywords: differential scanning calorimetry ; drug delivery ; long circulating liposomes ; mixed micelles ; NMR transverse relaxation ; phase separation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation. Methods. Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study. Results. Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol% of PEG(l,000–3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C16:0 to C14:0 caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C18:0. Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). Conclusions. These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016091314940
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    New Cationic Lipid Formulations for Gene Transfer (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1856-1860 
    Details
    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
    URL: http://dx.doi.org/10.1023/A:1016041326636
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of Non-Ionic Surfactants on the Formation of DNA/Emulsion Complexes and Emulsion-Mediated Gene Transfer (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1642-1646 
    Details
    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
    URL: http://dx.doi.org/10.1023/A:1016480421204
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    Paper (German National Licenses)
    Fulltext
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