Design, Characterization and Anti-Tumor Activity of Adriamycin-Containing Phospholipid Vesicles

  • Alberto Gabizon
  • Dorit Goren
  • Avner Ramu
  • Yechezkel Barenholz
Part of the NATO ASI Series book series (NSSA, volume 113)

Summary

In this report we describe the design of adriamycin (ADM)-containing liposome preparations aiming at optimization of various pre-established parameters. Regarding liposome composition phosphatidylserine (PS) and phosphatidylglycerol (PG) appear to be suitable negatively charged phospholipids which combined with phosphatidylcholine (PC) and cholesterol (CHOL), confer to liposomes high loading capacity for ADM and reasonable stability in plasma. Intravenous administration of these negatively-charged liposomes resulted in a favorable tissue distribution of ADM in both normal and tumor-bearing mice, characterized by decreased cardiac uptake of drug, and increased and sustained drug levels in the liver. Moreover, enhanced accumulation of drug also occurred in metastatic tumor cells isolated from the liver when ADM was injected in the liposome-associated form. This passive drug targeting resulted in an improved therapeutic efficiency of liposome-associated ADM in a tumor model of liver metastases. Liposome delivery of ADM was also shown to increase significantly its cytoreductive effect on spleen-infiltrating leukemia cells and to maintain the same cytoreductive efficiency on bone marrow residing leukemia cells with an overall favorable effect on survival in the BCL1 leukemia model. The reduction of ADM toxicity by liposome association together with the anti-tumor results indicate that liposomes represent a useful drug-delivery system for the treatment of major neoplastic conditions.

Keywords

Toxicity Leukemia Doxorubicin Methotrexate Cardiomyopathy 

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Alberto Gabizon
    • 1
  • Dorit Goren
    • 1
  • Avner Ramu
    • 1
  • Yechezkel Barenholz
    • 2
  1. 1.Hadassah University HospitalJerusalemIsrael
  2. 2.Hebrew University-Hadassah Medical SchoolJerusalemIsrael

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