Advertisement

Targeting of Liposomes: Study of Influencing Factors

  • Gregory Gregoriadis
  • Christopher Kirby
  • Pamela Large
  • Anne Meehan
  • Judith Senior
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 47)

Abstract

A decade has now elapsed since liposomes were first proposed1–3 as vehicles for drug delivery in biology and medicine. During this time extensive studies have revealed a multitude of uses4 and at the same time established many of the principles governing the system’s behaviour within the biological milieu.5–7 Among the advantages that liposomes offer as a drug carrier system, versatility in structural characteristics is most prominent. For instance, appropriate choice of lipid composition, size, surface charge and also of surface ligands that can recognise and associate with, target cells selectively can all profoundly influence the fate and behaviour of the carrier and thus contribute towards optimising the action of its drug contents. One of the major objectives in the use of liposomes in vivo is interaction with accessible cells i.e. those in the blood circulation, lining the capillaries and, in certain cases, cells in extravascular areas separated from the circulation by leaky membranes. There is, therefore, a need for drugs to be retained by the carrier for periods of time necessary for effective access to, and association with the target. Here we have attempted to understand factors that influence (a) quantitative retention of drugs by liposomes in vitro and in vivo (b) rates of liposome clearance from the circulation and (c) targeting of liposomes to specific cells.

Keywords

Cholesterol Content High Density Lipoprotein Drug Clearance Liposomal Drug Drug Retention 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    G. Gregoriadis and B.E. Ryman, Liposomes as carriers of enzymes or drugs: A new approach to the treatment of storage diseases, Biochem. J. 124: 58P (1971).Google Scholar
  2. 2.
    G. Gregoriadis and B.E. Ryman, Fate of protein-containing liposomes injected into rats. An approach to the treatment of storage diseases, Eur. J. Biochem. 24: 485 (1972).PubMedCrossRefGoogle Scholar
  3. 3.
    G. Gregoriadis and B.E. Ryman, Lysosomal localization of enzyme-containing liposomes injected into rats, Biochem. J. 128: 142 (1972).Google Scholar
  4. 4.
    G. Gregoriadis, Targeting of Drugs: Implications in Medicine, Lancet, 2: 241 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    G. Gregoriadis, The carrier potential of liposomes in Biology and Medicine, New Engl. J. Med. 295: 704 (1976).PubMedCrossRefGoogle Scholar
  6. 6.
    G. Gregoriadis, The carrier potential of liposomes in Biology and Medicine, New Engl. J. Med. 295: 765 (1976).PubMedCrossRefGoogle Scholar
  7. 7.
    B.E. Ryman and D.A. Tyrrell, Bags of potential, Essays Biochem. 16: 49 (1980).PubMedGoogle Scholar
  8. 8.
    G. Gregoriadis, Drug entrapment in liposomes, FEBS Lett., 36: 292 (1973).PubMedCrossRefGoogle Scholar
  9. 9.
    L. Krupp, A.V. Chobanian and I.P. Brecher, The in-vivo transformation of phospholipid vesicles to a particle resembling HDL in the rat, Biochem. Biophys. Res. Comm. 72: 1251 (1976).PubMedCrossRefGoogle Scholar
  10. 10.
    G. Scherphof, F. Roerdink, M. Waite and J. Parks, Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high density lipoproteins, Biochim. Biophys. Acta. 542: 296 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    T.M. Allen, A study of phospholipid interaction between high density lipoproteins and small unilamellar vesicles, Biochim. Biophys. Acta. 640: 385 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    C. Kirby, J. Clarke and G. Gregoriadis, Cholesterol content of small unilamellar liposomes controls phospholipid loss to high density lipoproteins in the presence of serum, FEBS Lett. 111: 324 (1980).PubMedCrossRefGoogle Scholar
  13. 13.
    C. Kirby and G. Gregoriadis, The effect of the cholesterol content of small unilamellar liposomes on the fate of their lipid components in vivo, Life Sciences, 27: 2223 (1980).PubMedCrossRefGoogle Scholar
  14. 14.
    L.S.S. Guo, R.L. Hamilton, J. Goerke, J.N. Weinstein and R.J. Havel, Interaction of unilamellar liposomes with serum lipoproteins and apolipoprotein, J. Lipid Res. 21: 993 (1980).PubMedGoogle Scholar
  15. 15.
    P.D. Ladbrooke, R.M. Williams and D. Chapman, Studies on lecithin-cholesterol-water interactions by differential scanning calorimetry and X-ray diffraction, Biochim. Biophys. Acta, 150: 333 (1968).PubMedCrossRefGoogle Scholar
  16. 16.
    R.A. Demel and B. Kruyff, The function of sterols in membranes, Biochim. Biophys. Acta. 457: 109 (1976).PubMedGoogle Scholar
  17. 17.
    D. Papahadjopoulos, K. Jacobson, S. Nir and T. Isac, Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol, Biochim. Biophys. Acta., 311: 330 (1973).PubMedCrossRefGoogle Scholar
  18. 18.
    G. Gregoriadis and C. Davis, Stability of liposomes in vivo and in vitro is promoted by their cholesterol content and the presence of blood cells, Biochem. Biophys. Res. Comm. 89: 1287 (1979).PubMedCrossRefGoogle Scholar
  19. 19.
    C. Kirby, J. Clarke and G. Gregoriadis, Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro, Biochem. J. 186: 591 (1980).PubMedGoogle Scholar
  20. 20.
    G. Gregoriadis and J. Senior, The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation, FEBS Lett. 119: 43 (1980).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Senior and G. Gregoriadis, Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components, (Submitted).Google Scholar
  22. 22.
    A.R. Tall, Studies on the transfer of phosphatidylcholine from unilamellar vesicles into plasma high density lipoproteins in the rat, J. Lipid Res., 21: 354 (1980).PubMedGoogle Scholar
  23. 23.
    G. Scherphof, J. Damen, D. Hoekstra, A.J.B.M. Van Renswoode and F.H. Roerdink, Fundamental studies on the cellular uptake of liposomes, in: “Cell Biological Aspects of Disease”, Th. W. Daems, E.H. Burger and B.A. Afzelius, eds., Leiden University Press, The Hague (1980).Google Scholar
  24. 24.
    C. Kirby and G. Gregoriadis, Plasma-induced release of solutes from small unilamellar liposomes is associated with pore formation in the bilayers. Biochem. J., 199: 251 (1981).PubMedGoogle Scholar
  25. 25.
    C. Kirby and G. Gregoriadis, The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection (Submitted).Google Scholar
  26. 26.
    D.S. Alberts, S.Y. Chang, H-S.G. Chen, T.E. Moon, T.L. Evans, R.L. Furner, K. Himmelstein and J.F. Gross, Kinetics of intravenous melphalan, Clin. Pharmacol. Ther., 26: 73 (1979).PubMedGoogle Scholar
  27. 27.
    R.L. Juliano and D. Stamp, Interactions of drugs with lipid membranes: Characteristics of liposomes containing polar or non-polar antitumour drugs, Biochim. Biophys. Acta., 586: 137 (1979).CrossRefGoogle Scholar
  28. 28.
    K.J. Huang, K-F.S. Luke and P.L. Beaumier, Hepatic uptake and degradation of unilamellar sphingomyelin/cholesterol liposomes: a kinetic study, Proc. Nat. Acad. Sci. USA, 77: 4030 (1980).CrossRefGoogle Scholar
  29. 29.
    C.D.V. Black and G. Gregoriadis, Interaction of liposomes with blood plasma proteins, Biochem. Soc. Trans., 4: 253 (1976).PubMedGoogle Scholar
  30. 30.
    D.A. Tyrrell, V.J. Richardson and B.E. Ryman, The effect of serum protein fractions on liposome-cell interactions in cultured cells and the perfused rat liver, Biochim. Biophys. Acta., 497: 469 (1977).PubMedCrossRefGoogle Scholar
  31. 31.
    G. Gregoriadis, D.E. Neerunjun and R. Hunt, Fate of a liposome-associated agent injected into normal and tumour bearing rodents. Attempts to improve localization in tumour tissues, Life Sciences, 21: 357 (1977).PubMedCrossRefGoogle Scholar
  32. 32.
    P. Large and G. Gregoriadis, The effect of storage on the stability of drug-containing small unilamellar liposomes (Submitted).Google Scholar
  33. 33.
    G. Gregoriadis and E.D. Neerunjun, Homing of liposomes to target cells, Biochem. Biophys. Res. Comm., 65: 537 (1975).PubMedCrossRefGoogle Scholar
  34. 34.
    V.P. Torchilin, V.G. Omel Yanenko, A.L. Klibanov, A.I. Michailov, V.I. Gol’Danskii and V.N. Smirhov, Incorporation of hydrophilic protein modified with hydrophobic agent into liposome membrane, Biochim. Biophys. Acta., 602: 511 (1980).PubMedCrossRefGoogle Scholar
  35. 35.
    P. Ghosh, P.K. Das and B.K. Bachhawat, Selective uptake of liposomes by different cell types of liver through the involvement of liposomal surface glycosides, Biochem. Soc. Trans., 9: 512 (1981).PubMedGoogle Scholar
  36. 36.
    A. Huang, L. Huang and S.J. Kennel, Monoclonal antibody covalently coupled with fatty acid, J. Biol. Chem. 255: 8015 (1980).PubMedGoogle Scholar
  37. 37.
    L.D. Leseruran, J. Barbet, F. Kourilsky and J.N. Weinstein, Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A, Nature, 288: 602 (1980).CrossRefGoogle Scholar
  38. 38.
    T.D. Heath, R.T. Fraley and D. Papahadjopoulos, Antibody targeting of liposomes: cell specificity obtained by conjugation of F(ab’)2 to vesicle surface, Science, 210: 539 (1980).PubMedCrossRefGoogle Scholar
  39. 39.
    V.K. Jansons and P.L. Mallett, Targeted liposomes: a method for preparation and analysis, Anal. Biochem. 111: 54 (1981).PubMedCrossRefGoogle Scholar
  40. 40.
    G. Gregoriadis, A. Meehan and M.M. Mah, Interaction of antibody-bearing small unilamellar liposomes with target free antigen in vitro and in vivo: Some influencing factors, Biochem. J. 200: 203 (1981).PubMedGoogle Scholar
  41. 41.
    G. Gregoriadis and A. Meehan, Interaction of antibody-bearing small unilamellar liposomes with antigen-coated cells: the effect of antibody and antigen concentration on the liposomal and cell surface respectively, Biochem. J. 200: 211 (1981).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Gregory Gregoriadis
    • 1
  • Christopher Kirby
    • 1
  • Pamela Large
    • 1
  • Anne Meehan
    • 1
  • Judith Senior
    • 1
  1. 1.Division of Clinical SciencesClinical Research CentreHarrow, Middx.UK

Personalised recommendations