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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 15 (1998), S. 1652-1656 
    ISSN: 1573-904X
    Schlagwort(e): antibodies ; drug clearance ; multivalency ; affinity ; titer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Pre-existing antibodies against a drug substance can significantly alter the pharmacokinetic profile of the drug in the circulation. Rapid clearance, mediated by complement or Fc receptors, occurs for crosslinked immune complexes, but not for complexes containing only one or two antibodies. With antibodies functioning as carrier proteins, monovalent antigens may enjoy a prolonged circulatory half-life, as observed in the case of digoxin, insulin, and various interleukins. While such an effect should be highly sensitive to fluctuations in antibody affinity and titer, it may present a means of extending the circulation of potent but rapidly cleared therapeutic agents. This mini-review attempts to delineate the causal relation between the factors influencing antibody binding and the circulatory life of a therapeutic agent, be it a small drug or a macromolecule.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 5 (1988), S. 352-358 
    ISSN: 1573-904X
    Schlagwort(e): human neutrophils ; phagocytosis ; fluid-phase pinocytosis ; particulate drug carriers ; liposomes ; lucifer yellow CH
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In assessing the feasibility of utilizing the phagocytic activity of polymorphonuclear leukocytes (PMNs) for a more efficient drug delivery to the cell, the uptake of the fluid-phase marker lucifer yellow CH (LY) at 37°C by human PMNs from LY-containing liposomes was compared with that from solutions. In the presence of 10% autologous serum, the LY uptake at 37°C via phagocytosis of LY-containing liposomes was generally two orders of magnitude greater than that via pinocytosis for a given PMN source when the concentrations of PMN, LY, and total lipid were in the range of 107 cells/ml, 0.5 mg/ml, and 50 µmol/ml, respectively. As expected, the LY uptake via phagocytosis was critically dependent upon the LY entrapment efficiency in the liposome preparation. Interestingly, little LY uptake was found when the serum was heat inactivated (56°C × 30 min). The serum effect was upon liposome vesicles rather than upon the cells. The present study demonstrates that the use of particular drug carriers for targeted drug delivery to PMNs and possibly to an extravascular site mediated by the cell infiltration is a viable approach.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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