Therapeutic Efficacy of Cytosine Arabinoside Trapped in Liposomes

  • E. Mayhew
  • Y. M. Rustum
  • F. Szoka
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 47)


A number of cancer chemotherapeutic agents have been encapsulated in liposomes and tested for their therapeutic effects (Kimelberg and Mayhew, 1978; Gregoriadis, 1979). However there have been few reports where direct comparisons of the therapeutic index of the liposome-entrapped drug and the free drug, administered under optimal conditions, have been made. There have been reports which indicate no increase in therapeutic effect for methotrexate (Kimelberg and Atchison, 1978; Kaye et al., 1980) or Actinomycin D (Kaye et al., 1979; Kaye and Ryman, 1980; Kedar et al., 1981) whereas increases in therapeutic index have been reported for adriamycin (Forssen and Tokes, 1979, 1981; Rahman et al., 1980, Olson et al., in press) after entrapment of these clinically useful drugs in liposomes.


Free Drug Therapeutic Index Roswell Park Memorial Institute Cytosine Arabinoside Mean Survival Time 
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  1. Ellens, H., Mayhew, E. and Rustum, Y., Reversible depression of the reticulo-endothelial system by liposomes, Biochim. Biophys. Acta. (submitted).Google Scholar
  2. Forssen, E.A. and Tokes, Z.A., 1979, In vitro and in vivo studies with adriamycin-liposomes, Biochem. Biophys. Res. Comm. 91: 1295.CrossRefGoogle Scholar
  3. Forssen, E.A. and Tokes, Z.A., 1981, Use of anionic liposomes for the reduction of chronic doxorubicin induced cardiotoxicity, Proc. Nat. Acad. Sci. U.S.A., 78: 1873.CrossRefGoogle Scholar
  4. Ganapathi, R., Krishan, A., Wodinsky, I., Zubrod, C.G. and Lesko, L.J., 1980, Effect of cholesterol content on antitumor activity and toxicity of liposome-encapsulated 1-p D-arabinofuranosylcytosine in vivo, Cancer Res., 40: 630.PubMedGoogle Scholar
  5. Gregoriadis, G., 1979, Liposomes in: “Drug Carriers in Biology and Medicine”, G. Gregoriadis, ed., Academic Press, London.Google Scholar
  6. Gregoriadis, G. and Neerunjun, D.E., 1974, Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats, Possible therapeutic applications, Eur. J. Biochem., 47: 179.PubMedCrossRefGoogle Scholar
  7. Gregoriadis, G., Neerunjun, D.E. and Hunt, R., 1977, Fate of a liposome-associated agent injected with normal and tumour-bearing rodents, Attempts to improve localization in tumour tissues, Life Sciences, 31: 357.CrossRefGoogle Scholar
  8. Gupta, C.M., Radhakrishnan, R. and Khorana, H.G., 1977, Glycerophospholipid syntheses: Improved general method and new analogs containing photoactivable groups, Proc. Nat. Acad. Sci. USA, 74: 4315.PubMedCrossRefGoogle Scholar
  9. Haynes, D.H. and Kang, C.H., 1978, Saturation of uptake of liposomes by the reticulo-endothelial system: possible use for increased tumor specificity, Ann. N.Y. Acad. Sci., 308: 440.Google Scholar
  10. Hunt, C.A., Rustum, Y.M., Mayhew, E. and Papahadjopoulos, D., 1979, Retention of cytosine arabinoside in mouse lung following intravenous administration in liposomes of different size, Drug Metabolism and Disposition, 7: 124.PubMedGoogle Scholar
  11. Kataoka, T. and Kobayaski, T., 1978, Enhancement of chemotherapeutic effect by entrapping 1 f3-D-arabinofuranosylcytosine in lipid vesicles and its mode of action, Ann. N.Y. Acad. Sci., 308: 387.PubMedCrossRefGoogle Scholar
  12. Kaye, S.B., Boden, J.A., Bagshaw, K.D. and Ryman, B.E., 1979, Effect of liposome encapsulation of actinomycin D on its therapeutic efficacy, Brit. J. Cancer, 40: 818.Google Scholar
  13. Kaye, S.B., Boden, J.A. and Ryman, B.E., 1980, Application of liposome entrapped cytotoxic drugs to the treatment in vivo of drug resistant solid murine tumors, Proc. Am. Assoc. Cancer Res., 21: 254.Google Scholar
  14. Kaye, S.B. and Ryman, B.E., 1980, The fate of liposome-entrapped actinomycin D in vivo and its therapeutic effect in a solid murine tumor, Biochem. Soc. Trans., 8: 107.PubMedGoogle Scholar
  15. Kedar, A., Mayhew, E., Moore, R.H. and Murphy, G.P., 1981, Failure of Actinomycin D entrapped in liposome to prolong survival in renal cell adenocarcinoma-bearing mice, Oncology, 38: 311.PubMedCrossRefGoogle Scholar
  16. Kimelberg, H.K. and Atchison, M.L., 1978, Effects of entrapment in liposomes on the distribution degradation and effectiveness of methotrexate in vivo, Ann. N.Y. Acad. Sci., 308: 395.PubMedCrossRefGoogle Scholar
  17. Kimelberg, H.K. and Mayhew, E., 1978, Properties and Biological effects of liposomes and their uses in pharmacology and toxicology in: “CRC Critical Reviews in Toxicology,” L. Goldberg, ed., CRC Press Inc., Florida.Google Scholar
  18. Mayhew, E., Papahadjopoulos, D., Rustum, Y.M. and Dave, C., 1978, Use of liposomes for the enhancement of the cytotoxic effects of cytosine arabinoside, Ann. N.Y. Acad. Sci., 308: 371.PubMedCrossRefGoogle Scholar
  19. Mayhew, E., Rustum, Y. and Szoka, F., 1980, Efficacy of liposome-entrapped cytosine arabinoside compared with infused free Ara-Cagainst L1210 tumor, Proc. Am. Assoc. Cancer Res., 21: 293.Google Scholar
  20. Mayhew, E., Rustum, Y.M., Szoka, F. and Papahadjopoulos, D., 1979, Role of cholesterol in enhancing the antitumor activity of cytosine arabinoside entrapped in liposomes, Cancer Treatment Reports, 63: 1923.PubMedGoogle Scholar
  21. Olson, F., Mayhew, E., Maslow, D., Rustum, Y. and Szoka, F., 1982, Characterization, toxicity and therapeutic efficacy of adriamycin encapsulated in liposomes, Eur. J. Cancer.Google Scholar
  22. Rahman, A., Kessler, A., More, N., Silkie, B., Rowden, G., Woolley, P. and Schein, P.S., 1980, Liposomal protection of adriamycininduced cardiotoxocity in mice, Cancer Res., 40: 1532.PubMedGoogle Scholar
  23. Rahman, Y.E. and Wright, B.J., 1975, Liposomes containing chelating agents, Cellular penetration and a possible mechanism of metal removal, J. Cell. Biol., 65: 112.PubMedCrossRefGoogle Scholar
  24. Rustum, Y.M., Dave, D., Mayhew, E. and Papahadjopoulos, D., 1979, Role of liposome type and route of administration in the antitumor activity of liposome-entrapped 1 /3-D-arabinofuranosylcytosine against mouse L1210 leukemia, Cancer Res., 39: 1390.PubMedGoogle Scholar
  25. Semon, J.H. and Grindey, G.B., 1978, Potentiation of the Anti-tumor activity of Methotrexate by Concurrent Infusion ofThymidine, Cancer Res., 38: 2405.Google Scholar
  26. Skipper, H.E., Schabel, F.M., Jr. and Wilcox, W.S., 1967, Experimental evaluation of potential anticancer agents, XXI. Scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells, Cancer Chemotherapy Reports, 51: 125.Google Scholar
  27. Szoka, F. and Papahadjopoulos, D., 1978, Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation, Proc. Nat. Acad. Sci. U.S.A., 75: 4194.CrossRefGoogle Scholar
  28. Szoka, F., Olson, F., Heath, T., Vail, W., Mayhew, E. and Papahadjopoulos, D., 1980, Preparation of unilamellar liposomes of intermediate size by a combination of reverse phase evaporation and extrusion through poly-carbonate membranes, Biochim. Biophys. Acta, 601: 559.PubMedCrossRefGoogle Scholar
  29. Wisse, E., Gregoriadis, G. and Deams, W.T., 1976, Electron microscopic cytochemical localization of intravenously injected liposome-encapsulated horseradish peroxidase in rat liver cells, Adv. Exp. Med. Biol., 73: 237.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • E. Mayhew
    • 1
  • Y. M. Rustum
    • 2
  • F. Szoka
    • 1
  1. 1.Department of Experimental PathologyRoswell Park Memorial InstituteBuffaloUSA
  2. 2.Department of Experimental Therapeutics and Grace Cancer Drug CenterRoswell Park Memorial InstituteBuffaloUSA

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