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Clearance and maximum removal rate of liposomes in normal and impaired liver of rat

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Summary

In the present study the author described a new method for analysis of the reticuloendothelial system (RES) function, using blood clearance of liposomes containing encapsulated phenolsulfonphthalein as a marker. Various types and doses of liposomes were intravenously administered to rats and the clearance of liposomes from blood was observed. Large liposomes were cleared from blood at a faster rate than small ones. Large liposomes composed of phosphatidylcholine and cholesterol were mainly phagocytized with Kupffer cells. The rate of disappearance of liposomes from blood was able to be calculated. With increments of administered doses there was an associated decrease of the disappearance rate, which corresponded to the Lineweaver-Burk plot in the enzymatic process, and it was possible to calculate the maximum removal rate and Michaelis constant. Disappearance rates decreased after prior administration of large liposomes and the inhibitory mode was competitive. Disappearance rates decreased after pretreatment with dextran sulfate and the inhibitory mode differed from the competitive. In partially hepatectomized and CC14 intoxicated animals, disappearance rates also decreased.

Liposomes are easily prepared and non-toxic. The clearance test of liposomes is possible to evaluate the role of the phagocytic function of the RES, chiefly Kupffer cells, in various experimental and clinical conditions.

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References

  1. Bangham AD: Membrane models with phospholipids. Progr Biophys Mol Biol 18: 29, 1968

    Article  CAS  Google Scholar 

  2. Rahman YE, et al: Liposomes containing chelating agents. J Cell Biol 65: 112, 1975

    Article  PubMed  CAS  Google Scholar 

  3. Wisse E, et al: Electron microscopic cytochemical loc alization of intravenously injected liposome-encapsulated horseradish peroxidase in rat liver cells, in “The Reticuloendothelial System in Health and Disease”, by Reichard SM, Escobar MR, Friedman H. Plenum Publishing Corporation, New York, 1976, p 237

    Google Scholar 

  4. Bradfield JWB: Can we measure Kupffer cell function in man?, in “The Reticuloendothelial System and the Pathogenesis of Liver Disease”, by Liehr H, Grün M. Elsevier, North-Holland, 1980, p 309

    Google Scholar 

  5. Szoka F, et al: Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA 75:4194, 1978

    Article  PubMed  CAS  Google Scholar 

  6. Kirby C, et al: Effect of cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro. Biochem J 186: 591, 1980

    PubMed  CAS  Google Scholar 

  7. Bøyum A: Separation of white blood cells. Nature 204: 793, 1964

    Article  PubMed  Google Scholar 

  8. Higgins GM, et al: Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12: 186, 1931

    Google Scholar 

  9. Benacerraf B, et al: Physiology of phagocytosis of particles by the R.E.S., in “Physiopathology of the Reticuloendothelial System”, by Halpern BN. Blackwell Scientific Publications, Oxford, 1957, p 52

    Google Scholar 

  10. Segal AW, et al: Morphological observations on the cellular and subcellular destination of intravenously administered liposomes. Br J Exp Path 55: 320, 1974

    CAS  Google Scholar 

  11. Gregoriadis G, et al: Control of the rate of hepatic up take and catabolism of liposome-entrapped proteins injected into rats. Possible therapeutic applications. Eur J Biochem 47: 179, 1974

    Article  PubMed  CAS  Google Scholar 

  12. Juliano RL, et al: The effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs. Biochem Biophy Res Commun 63: 651, 1975

    Article  CAS  Google Scholar 

  13. Hart IR, et al: Toxicity studies of liposome-encapsulated immunomodulators administered intravenously to dogs and mice. Cancer Immunol Immunother 10: 157, 1981

    Article  CAS  Google Scholar 

  14. Saba TM: Physiology and physiopathology of the reticuloendothelial system. Arch Intern Med 126: 1031, 1970

    Article  PubMed  CAS  Google Scholar 

  15. Wisse E: An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. J Ultrastruc Res 31: 125, 1970

    Article  CAS  Google Scholar 

  16. Rahman YE, et al: Differential uptake by liposomes varying in size and lipid composition by parenchymal and Kupffer cells of mouse liver. Life Sci 31: 2061, 1982

    Article  PubMed  CAS  Google Scholar 

  17. Jonah MM, et al: Tissue distribution of EDTA encapsulated within liposomes of varying surface properties. Biochim Biophys Acta 401: 336, 1975

    Article  PubMed  CAS  Google Scholar 

  18. Paumgartner G, et al: Kinetics of indocyanine green removal from the blood. Ann NY Acad Sci 170: 134, 1970

    Article  CAS  Google Scholar 

  19. Caride VJ, et al: Evaluation of liposome-entrapped radioactive tracers as scanning agents. Part 1: Organ distribution of liposome [99mTc-DTPA] in mice. J Nucl Med l7: 1067, 1976

    Google Scholar 

  20. Kao YJ, et al: Interactions of liposomes with the reticuloendothelial system. Effects of reticuloendothelial blockade of the clearance of large unilamellar vesicles. Biochim Biophys Acta 677: 453, 1981

    PubMed  CAS  Google Scholar 

  21. Ellens H, et al: Reversible depression of the reticuloendothelial system by liposomes. Biochim Biophys Acta 714: 479, 1982

    PubMed  CAS  Google Scholar 

  22. Bradfield JWB, et al: The mechanism of the adjuvant effect of dextran sulfate. Immunology 26: 383, 1974

    PubMed  CAS  Google Scholar 

  23. Saba TM: Plasma fibronectin and hepatic Kupffer cell function, in “Progress in Liver Diseases” Vol VII, by Popper H, Schaffner F. Grime & Stratton, New York, 1982,p 109

    Google Scholar 

  24. Saba TM: Liver blood flow and intravascular colloid clearance alterations following partial hepatectomy. J Reticuloendothel Soc 7: 406, 1970

    PubMed  CAS  Google Scholar 

  25. Leong GF, et al: Liver function in regenerating rat liver. CrPO4 colloid uptake and bile flow. Fed Proc 17: 388, 1958

    Google Scholar 

  26. Juliano, et al: The interaction of plasma proteins with liposomes: Protein binding and effects on the clotting and complements systems, in “Liposomes and Immunobiology”, by Baldwin HT, Howard RS. Elsevier, North-Holland, 1980, p 49

    Google Scholar 

  27. Hsu MJ, et al: Interactions of liposomes with the reticuloendothelial system. II: Nonspecific and receptormediated uptake of liposomes by mouse peritoneal macrophages. Biochim Biophys Acta 720: 411, 1982

    Article  PubMed  CAS  Google Scholar 

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Ogiwara, M. Clearance and maximum removal rate of liposomes in normal and impaired liver of rat. Gastroenterol Jpn 19, 34–40 (1984). https://doi.org/10.1007/BF02774644

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  • DOI: https://doi.org/10.1007/BF02774644

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