Therapeutic Potential of Liposomes as Carriers in Leishmaniasis, Malaria, and Vaccines

  • Carl R. Alving
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 47)


Since the first suggestion, approximately ten years ago, that lipid vesicles might have practical uses in medicine, liposomes have been a treatment in search of a disease. The approach of my laboratory since 1976 has been to search for clinical applications among infectious diseases. Because parenterally injected liposomes natually travel in great amounts to the liver and spleen I felt, at least at the beginning of our research, that attempts to tailor liposomes to particular diseases by artificially targeting the vesicles to areas other than the liver and spleen, might be difficult. Therefore, my colleagues and I have concentrated only on diseases in which the liver and spleen play an important, or even a crucial, role.


Visceral Leishmaniasis Cholera Toxin Adjuvant Effect Plasmodium Berghei Walter Reed Army Institute 
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  1. 1.
    H. C. Goodman, Immunology and tropical diseases: Challenges and opportunities, Ann. Immunol. (Inst. Pasteur) 129C: 267 (1978)Google Scholar
  2. 2.
    C. R. Alving, E. A. Steck, W. L. Chapman, Jr., V. B. Waits, L. D. Hendricks, G. M. Swartz, Jr., and W. L. Hanson, Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs, Proc. Natl. Acad. Sci. U.S.A. 75: 2959 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    C. R. Alving, E. A. Steck, W. L. Hanson, P. S. Loizeaux, W. L. Chapman, Jr., and V. B. Waits, Improved therapy of experimental leishmaniasis by use of a liposome-encapsulated antimonial drug, Life Sci. 22: 1021 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    C. R. Alving, E. A. Steck, W. L. Chapman, Jr., V. B. Waits, L. D. Hendricks, G. M. Swartz, Jr., and W. L. Hanson, Liposomes in leishmaniasis: Therapeutic effects of antimonial drugs, 8-aminoquinolines, and tetracycline, Life Sci. 26: 2231 (1980).PubMedCrossRefGoogle Scholar
  5. 5.
    C. R. Alving and E. A. Steck, The use of liposome-encapsulated drugs in leishmaniasis, Trends Biochem. Sci. 4 (8): N175 (1979).Google Scholar
  6. 6.
    C. R. Alving, I. Schneider, G. M. Swartz, Jr., and E. A. Steck, Sporozoite-induced malaria: Therapeutic effects of glycolipids in liposomes, Science 205: 1142 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    C. R. Alving, Immune reactions of lipids and lipid model membranes, in:“The Antigens, vol. 4”, M. Sela, ed., Academic Press, NY, p.1 (1977).Google Scholar
  8. 8.
    B. G. Schuster, M. Neidig, B. M. Alving, and C. R. Alving, Production of antibodies against phosphocholine, phosphatidylcholine, sphingomyelin, and lipid A by injection of liposomes containing lipid A, J. Immunol. 122: 900 (1979).PubMedGoogle Scholar
  9. 9.
    C. R. Alving, Liposomes as vehicles for vaccines, in:“New Developments With Human and Veterinary Vaccines”, A. Mizrahi, M. A. Klingberg, I. Hertman, and A. Kohn, eds., Alan R. Liss, Inc., NY, (1980).Google Scholar
  10. 10.
    C. R. Alving, B. Banerji, J. Clements, and R. L. Richards, Adjuvanticity of lipid A and lipid A fractions in liposomes, in:“Liposomes and Immunobiology”, B. H. Tom and H. R. Six, eds., Elsevier/North-Holland, NY, (1980).Google Scholar
  11. 11.
    R. K. Sanyal and R. R. Arora, Assessment of drug therapy of kala-azar in current epidemic in Bihar, J. Com. Dis. 11: 198 (1979).Google Scholar
  12. 12.
    C. D. V. Black, G. J. Watson, and R. J. Ward, The use of Pentostam liposomes in the chemotherapy of experimental leishmaniasis, Trans. R. Soc. Trop. Med. Hyg. 71: 550 (1977).PubMedCrossRefGoogle Scholar
  13. 13.
    R. R. C. New, M. L. Chance, S. C. Thomas, and W. Peters, Antileishmanial activity of antimonials entrapped in liposomes, Nature 272: 55 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    W. H. Wernsdorfer, Long-term aims of malaria research, Trends Biochem. Res. 4 (3): N49 (1979)Google Scholar
  15. 15.
    P. Pirson, R. F. Steiger, A. Trouet, J. Gillet, and F. Herman, Primaquine liposomes in the chemotherapy of experimental murine malaria, Ann. Trop. Med. Parasit. 74: 383 (1980).PubMedGoogle Scholar
  16. 16.
    G. Ashwell and A. G. Morell, The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins, Adv. Enzymol. 41: 99 (1974).Google Scholar
  17. 17.
    A. Surolia and B. K. Bachhawat, Monosialoganglioside liposome-entrapped enzyme uptake by hepatic cells. Biochim. Biophys. Acta 497: 760 (1977).PubMedCrossRefGoogle Scholar
  18. 18.
    M. M. Jonah, E. A. Cerny, and Y. E. Rahman, Tissue distribution of EDTA encapsulated within liposomes containing glycolipids or brain phospholipids, Biochim. Biophys. Acta 541: 321 (1978).CrossRefGoogle Scholar
  19. 19.
    J. R. Riordan, L. Mitchell, and M. Slavik, The binding of asialo-glycoprotein to isolated Golgi apparatus, Biochem. Biophys. Res. Comm. 59: 1373 (1974).CrossRefGoogle Scholar
  20. 20.
    W. E. Pricer, Jr. and G. Ashwell, Subcellular distribution of a mammalian hepatic binding protein specific for asialoglycoproteins, J. Biol. Chem. 251: 7539 (1976).PubMedGoogle Scholar
  21. 21.
    H. D. Danforth, M. Aikawa, A. H. Cochrane, and R. S. Nussenzweig, Sporozoites of mammalian malaria: Attachment to, interiorization and fate within macrophages, J. Protozool. 27: 193 (1980).PubMedGoogle Scholar
  22. 22.
    I. Schneider, and C.R. Alving, unpublished data.Google Scholar
  23. 23.
    R. F. Steiger, D. G. Layton, P. Pirson, J. Gillet, and F. Herman, Therapeutic activity of DAPI on experimental murine malaria, J. Parasitol. 66: 352 (1980).CrossRefGoogle Scholar
  24. 24.
    B. H. Tom, An overview: Liposomes and immunobiology-macrophages, liposomes and tailored immunity, in:“Liposomes and Immunobiology”, B. H. Tom and H. R. Six, eds., Elsevier, North-Holland, NY, (1980).Google Scholar
  25. 25.
    C. R. Alving, J. J. Mooney, and G. E. Olson, Use of liposomes as a model for studying immune phagocytosis, Fed. Proc. 30: 693 (1971).Google Scholar
  26. 26.
    N. van Rooijen and R. van Nieuwmegen, Immunoadjuvant properties of liposomes, this volume.Google Scholar
  27. 27.
    B. Banerji and C. R. Alving, Anti-liposome antibodies induced by lipid A. I. Influence of ceramide, glycosphingolipids, and phosphocholine on complement damage, J. Immunol. 126: 1080 (1981).PubMedGoogle Scholar
  28. 28.
    J. M. Chiller, B. J. Skidmore, D. C. Morrison, and W. O. Weigle, Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity, Proc. Natl. Acad. Sci. U.S.A. 70: 2129 (1973).PubMedCrossRefGoogle Scholar
  29. 29.
    Y. Cho, K. Tanamoto, Y. Oh, and J. Y. Homma, Differences of chemical structures of Pseudomonas aeruginosa lipopolysaccharide essential for adjuvanticity and antitumor and interferon-inducing activities, FEBS Lett. 105: 120 (1979).PubMedCrossRefGoogle Scholar
  30. 30.
    B. Banerji and C. R. Alving, Lipid A from endotoxin: Antigenic activities of purified fractions in liposomes, J. Immunol. 123: 2558 (1979)PubMedGoogle Scholar
  31. 31.
    K. Uemura, R. A. Nicolotti, H. R. Six, and S. C. Kinsky, Antibody formation in response to liposomal model membranes sensitized with N-substituted phosphatidylethanolamine derivatives, Biochemistry 13: 1572 (1974).PubMedCrossRefGoogle Scholar
  32. 32.
    F. Roerdink, B. J. Berson, R. L. Richards, G. M. Swartz, Jr., J. A. Lyon, and C. R. Alving, Specificity of a hybridoma monoclonal antibody against liposomes containing phosphatidylinositol monophosphate, Fed. Proc. 40: 996 (1981).Google Scholar
  33. 33.
    R. L. Friedman, F. Roerdink, B. H. Iglewski, and C. R. Alving, Suppression of cytotoxicity of diphtheria toxin by monoclonal antibodies against phosphatidylinositol phosphate, Biophys. J, in pressGoogle Scholar
  34. 34.
    G. H. Strejan, P. M. Smith, C. W. Grant, and D. Surlan, Naturally occurring antibodies to liposomes. I. Rabbit antibodies to sphingomyelin-containing liposomes before and after immunization with unrelated antigens, J. Immunol. 123: 370 (1979).PubMedGoogle Scholar
  35. 35.
    R. L. Richards and C. R. Alving, Immune reactivities of antibodies against glycolipids. Natural Antibodies, in:“Cell Surface Glycolipids”, ACS Symposium Series No. 128, C. C. Sweeley, ed., American Chemical Society, Washington, (1980).CrossRefGoogle Scholar
  36. 36.
    R. L. Richards and C. R. Alving, unpublished data.Google Scholar
  37. 37.
    C. R. Alving, J. Moss, R. L. Richards, and L. I. Alving, Liposomes as vehicles for vaccines. Increased antigenicity and lack of toxicity of a toxin bound to liposomes, Clin. Res. 29 (2): 531A (1981).Google Scholar
  38. 38.
    N. van Rooijen and R. van Nieuwmegen, Liposomes in immunology: evidence that their adjuvant effect results from surface exposition of the antigens, Cell. Immunol. 49: 402 (1980).Google Scholar
  39. 39.
    D. C. Morrison, R. J. Ulevitch, The effects of bacterial endotoxins on host mediation systems, Am. J. Pathol. 93: 525 (1978).Google Scholar
  40. 40.
    R. B. Ramsey, M. B. Hamner, B. M. Alving, J. S. Finlayson, C. R. Alving, Effects of lipid A and liposomes containing lipid A on platelet and fibrinogen production in rabbits, Blood 56: 307 (1980).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Carl R. Alving
    • 1
  1. 1.Department of Membrane BiochemistryWalter Reed Army Institute of ResearchUSA

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