Effect of cholesterol on the uptake and intracellular degradation of liposomes by liver and spleen: A combined biochemical and γ-ray perturbed angular correlation study

F.H Roerdink*, J Regts, T Handel, S.M Sullivan, J.D Baldeschwieler, G.L Scherphof

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    31 Citaten (Scopus)

    Samenvatting

    We investigated the effect of cholesterol on the uptake and intracellular degradation of liposomes by rat liver and spleen macrophages. Multilamellar vesicles (MLV) consisting of distearoylphosphatidylcholine/phosphatidylserine (molar ratio 9:1) or distearoylphosphatidylcholine/cholesterol/phosphatidylserine (molar ratio 4:5:1) were labeled with [3H]cholesteryl hexadecyl ether and/or cholesteryl [14C]oleate. After i.v. injection the cholesterol-containing liposomes were eliminated less rapidly from the bloodstream and taken up to a lesser extent by the liver (macrophages) than the cholesterol-free liposomes. Assessment of the 3H/14C ratios in liver and spleen cells revealed that the cholesterol-containing liposomes are substantially more resistant towards intracellular degradation than the cholesterol-free liposomes. These results could be confirmed by measuring the release of 111In from liposomes after uptake by liver and spleen by means of γ-ray perturbed angular correlation spectroscopy. Experiments with cultured Kupffer cells in monolayer also revealed that incorporation of cholesterol results in a decrease of the uptake and an increase of the intracellular stability of cholesteryl [14C]oleate-labeled liposomes. Finally, incubation of both types of liposomes with lysosomal fractions prepared from rat liver demonstrated a difference in susceptibility to lysosomal degradation: the cholesterol-free vesicles were much more sensitive to lysosomal esterase than the cholesterol-containing liposomes. These results may be relevant to the application of liposomes as a drug carrier system to liver and spleen (macrophages)
    Originele taal-2English
    Pagina's (van-tot)234-240
    Aantal pagina's7
    TijdschriftBiochimica et biophysica acta
    Volume980
    Nummer van het tijdschrift2
    DOI's
    StatusPublished - 14-apr-1989

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