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Cell Surface Effects of Adriamycin and Carminomycin Immobilized on Cross-Linked Polyvinyl Alcohol¹

Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 [L. B. W., K. A. E.], and Department of Pharmacology, College of Medicine, University of Vermont, Burlington, Vermont 05405 [T. R. T.]

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. In the present work, 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 three immobilized drug preparations inhibited the growth of L1210 or S180 clones following 2- or 20-h incubation with cells at 37°C. The results strongly support the concept that immobilized anthracyclines can be cytotoxic to cultured cells, for at least two different orientations of the drug on the support.

¹ This work was supported in part by grants from the American Cancer Society (IN-58S, CH-212), the Samuel and Emma Winters Foundation, and the NIH (RR05416, CA28852).

² To whom requests for reprints should be addressed, at Department of Pharmacology, School of Medicine, University of Pittsburgh, 518 Scaife Hall, Pittsburgh, PA 15261.

³ Recipient of a research career development award (CA00684).

Received 9/28/84. Revised 2/25/85. Accepted 5/10/85.

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