CELL-SURFACE EFFECTS OF ADRIAMYCIN AND CARMINOMYCIN IMMOBILIZED ON CROSS-LINKED POLYVINYL-ALCOHOL

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (8) , 3529-3536
Abstract
Previous reports have claimed Adriamycin to be cytotoxic to cultured tumor cells when the drug is covalently immobilized on a solid support, thus suggesting a cell surface mechanism of action for the drug. Although these previous reports attempted to rule out released drug or endocytosis of drug-support particles as alternative explanations for the observed cytotoxicity, a more thorough analysis is necessary to substantiate fully the cell surface idea. The stability of the drug-support linkage was increased by use of cross-linked polyvinyl alcohol as the support and cyanuric chloride or a diazonium salt for attachment of the drug. Different anthracycline orientations were tested by coupling Adriamycin at the amino sugar and carminomycin at the D-ring. The Adriamycin cross-linked polyvinyl alcohol and carminomycin cross-linked polyvinyl alcohol preparations had much lower drug release rates than did the earlier used carbamate-linked Adriamycin cross-linked agarose materials. All 3 immobilized drug preparations inhibited the growth of L1210 [mouse leukemia] or S180 [mouse sarcoma] clones following 2- or 20-h incubation with cells at 37.degree. C. Immobilized anthracyclines can be cytotoxic to cultured cells, for at least 2 different orientations of the drug on the support.