SELECTIVE DELIVERY OF LIPOSOME-ASSOCIATED CIS-DICHLORODIAMMINEPLATINUM(II)BY HEAT AND ITS INFLUENCE ON TUMOR DRUG UPTAKE AND GROWTH

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (5) , 1602-1607
Abstract
To optimize the chemotherapeutic treatment of mouse tumor sarcoma 180 cells, liposomes containing cis-dichlorodiammineplatinum(II) (PDD), having transition temperatures a few degrees higher than the rectal temperature of mice, were used in combination with local hyperthermia. The uptake of radioactive PDD by tumors heated for 1 h at 42.degree. was almost 4-fold greater when the drug was associated in liposomes than if administered as free drug. Uptake of liposome-administered radioactive Pt by liver was twice that obtained with free PDD; its incorporation by the kidney was the same by either method of drug administration. The effect of various combinations of hyperthermia, drug-containing liposomes and free PDD on tumor growth was also studied. Treatment with liposome-associated PDD plus local heating resulted in a dose-modifying factor of 7 when compared with free drug and no hyperthermia. The dose-modifying factor was 2.5 when PDD liposomes and heat were compared with free drug and heat. Thus, PDD could be specifically released from liposomes by heat and resulted in a greater drug uptake and a delayed tumor growth following treatment. Potential normal tissue toxicity problems still need to be resolved before clinical application of this combined modality will be possible.