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Liposomes as a Drug Delivery System: Optimization Studies

  • Gregory Gregoriadis
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

The great structural versatility of liposomes, their relatively inoccuous nature and ability to incorporate a wide spectrum of biologically active agents have led to the adoption of the system by numerous workers as a drug carrier.1,2 Proposed applications2 for liposome-mediated drug delivery include antimicrobial3 and cancer therapy,4 metal detoxification,5 oral adminstration of hormones, enzymes and other drugs which are either unstable in or unabsorbable by the gut,6 vaccines,7 activation of macrophages,8 ligand-mediated targeting to accessible cells in vivo,9 topical uses of drugs (eg, skin and eye diseases)10 and as a substitute for red blood cells (haemosomes).11 Some of these applications seem realistic enough for early clinical development, whilst others must await further advances.2 In parallel, there has been considerable progress in liposome technology1 and related achievements have ensured in many cases adoption of the liposome system by the Industry.12 Technological achievements in this area include development of methods for high yield drug entrapment, achieving a relatively low lipid:drug ratio.1

Keywords

High Density Lipoprotein Phospholipid Molecule Small Unilamellar Vesicle Solute Retention Solute Loss 
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.

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References

  1. 1.
    G. Gregoriadis (Ed.) “Liposome Technology” Vols. I–III, CRC Press Inc., Boca Raton (1984).Google Scholar
  2. 2.
    G. Gregoriadis (Ed.) “Liposomes as Drug Carriers: Recent Trends and Progress”, John Wiley and Sons, Chichester (1988).Google Scholar
  3. 3.
    G. Lopez-Berestein, V. Fainstein, R. Hopfer, K. Mehta, M.P. Sullivan, M. Keating, M.G. Rosenblum, R. Mehta, M. Luna, E.M. Hersh, J. Reuben, R.L. Juliano and G.P. Bodey, Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: A preliminary study, J. Infect. Dis., 151:704 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Rahman, A. Joher and J.R. Neefe, Immunotoxicity of multiple dosing regiments of free doxorubicin entrapped in cardiolipin liposomes, Br. J. Cancer, 54:401 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    Y.E. Rahman, Liposomes and chelating agents, in: “Liposomes in Biological Systems”, G. Gregoriadis, ed., John Wiley, Chichester (1980).Google Scholar
  6. 6.
    M. Nagata, T. Yotsuyanegi, M. Nonomura and K. Ikeda, Coagulation recovery after warfarin-induced hypoprothrombinaemia by oral administration of liposomally-associated vitamin K to rabbits, J.Pharm.Pharmacol., 36:527 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    G. Gregoriadis, Liposomes as carriers for drugs and vaccines, Trends in Biotechnology, 3:235 (1985)CrossRefGoogle Scholar
  8. 8.
    I.J. Fidler and G. Poste, Macrophage-mediated destruction of malignant tumour cells and new strategies for the therapy of metastatic disease, Springer Seminar Immunopath., 5:161 (1982).Google Scholar
  9. 9.
    B. Wolff and G. Gregoriadis, The use of monoclonal anti-Thy1 IgG1 for the targeting of liposomes to AKR-A cells in vitro and in vivo, Biochim. Biophys. Acta, 802:259 (1984).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Mezei and V. Gulasekharam, Liposomes: A selective drug delivery system for the topical route of administration, Life Sci., 26:1473 (1980).PubMedCrossRefGoogle Scholar
  11. 11.
    J.A. Hayward, D.M. Levine, L. Neufeld, S.R. Simon, D.S. Johnston and D. Chapman, Polymerized liposomes as stable oxygen-carriers, FEBS Lett., 187:261 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    G. Maierhofer, Liposomes: Preparation and application, International Laboratory, 15:92 (1985).Google Scholar
  13. 13.
    C. Kirby and G. Gregoriadis, Dehydration-rehydration vesicles (DRV): A new method for high yield drug entrapment in liposomes, Biotechnology, 2:979 (1984).CrossRefGoogle Scholar
  14. 14.
    G. Gregoriadis, Liposomal subunit vaccine against Epstein-Barr virus-induced malignant lymphoma, Nature, 320:87 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    G. Gregoriadis, D. Davis and A. Davies, Liposomes as immunological adjuvants: Antigen incorporation studies, Vaccine, 5:143 (1987).CrossRefGoogle Scholar
  16. 16.
    D. Davis and G. Gregoriadis, Liposomes as adjuvants with immunopurified tetanus toxoid: influence of liposomal characteristics, Immunology, 61:229 (1987).PubMedGoogle Scholar
  17. 17.
    D. Davis, A. Davies and G. Gregoriadis, Liposomes as immunological adjuvants with immunopurified tetanus toxoid: The immune response, Immunol. Lett., 14:341 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    P.A.H.M. Toonen and D.J.A. Crommelin, Immunoglobulins as targeting agents for liposome-encapsulated drugs, Pharmaceutisch Weekblad Scient. Edn., 5:269 (1983).CrossRefGoogle Scholar
  19. 19.
    L.M. Crowe, J.H. Crowe, A. Rudolph, C. Womersley and L. Appel, Preservation of freeze-dried liposomes by trehalose, Arch. Biochem. Biophys., 242:240 (1985).PubMedCrossRefGoogle Scholar
  20. 20.
    G. Gregoriadis, Targeting of drugs with molecules, cells and liposomes, Trends Pharm. Sci., 4:304 (1983).CrossRefGoogle Scholar
  21. 21.
    J. Senior, Fate and behaviour of liposomes in vivo: A review of controlling factors, CRC Crit. Rev. Therapeutic Drug Carrier Systems, 3:123 (1987).Google Scholar
  22. 22.
    G. Gregoriadis, Fate of injected liposomes: Observation on entrapped solute retention, vesicle clearance and tissue distribution in vivo, in: “Liposomes as Drug Carriers: Recent Trends and Progress”, G. Gregoriadis, ed., John Wiley and Sons, Chichester (1988).Google Scholar
  23. 23.
    C. Kirby and G. Gregoriadis, The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice, Biochem. Pharmacol., 32:609 (1983).PubMedCrossRefGoogle Scholar
  24. 24.
    L. Krupp, A.V. Chobanian and J.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
  25. 25.
    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
  26. 26.
    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. Biophy. Acta, 542:296 (1978).CrossRefGoogle Scholar
  27. 27.
    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 Sci., 27:2223 (1980).PubMedCrossRefGoogle Scholar
  28. 28.
    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
  29. 29.
    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., 89:925 (1979).CrossRefGoogle Scholar
  30. 30.
    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).Google Scholar
  31. 31.
    J. Senior, J.C. W. Crawley and G. Gregoriadis, Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection, Biochim. Biophys. Acta, 839:1 (1985).PubMedCrossRefGoogle Scholar
  32. 32.
    G. Gregoriadis and B.E. Ryman, Lysosomal localization of β-fructofuranosidase-containing liposomes injected into rats. Some implications in the treatment of genetic disorders, Biochem. J., 129:123 (1972).PubMedGoogle Scholar
  33. 33.
    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
  34. 34.
    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, Life Sci., 30:2123 (1982).PubMedCrossRefGoogle Scholar
  35. 35.
    J. Senior and G. Gregoriadis, Is half-life of circulating small unilamellar liposomes determined by changes in their permeability? FEBS Lett., 145:109 (1982).PubMedCrossRefGoogle Scholar
  36. 36.
    G. Gregoriadis and J. Senior, Targeting of small unilamellar liposomes to the galactose receptor in vivo, Biochem. Soc. Trans., 12:337 (1984).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Gregory Gregoriadis
    • 1
  1. 1.Medical Research Council Group Academic Department of MedicineRoyal Free Hospital School of MedicineLondonUK

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