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Synthesis, Characterization and Antitumor Activity of Macromolecular Prodrugs of Adriamycin

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Recent Advances in Drug Delivery Systems

Abstract

The anthracycline antibiotics daunomycin and 14-hydroxydaunomycin (adriamycin) have been shown to be very effective in the treatment of a number of malignancies (1). Besides the non-specific side-effects of cytostatic agents, adriamycin exerts a specific toxic activity on the heart (2). This side effect may eventually lead to a life-threatening congestive heart failure when a cumulative dose of 550 mg.m-2 has been exceeded. Although the exact mechanism through which toxicity develops has not been elucidated, three major hypotheses on the pathogenesis of adriamycin induced cardiotoxicity have been postulated. As all quinones, adriamycin is a potent chelating agent for divalent cations, in particular for Ca2+ which is involved in the excitation-contraction coupling of muscle cells (3). Adriamycin can be converted to a semi-quinone either by microsomal or by mitochondrial metabolic pathways. These semiquinones give rise to the formation of free radicals, which may lead to peroxidation of polyunsaturated fatty acid structures (4). Finally, adriamycin is a strong intercalating agent, which causes an inhibition of RNA, DNA protein synthesis. Inhibition of the synthesis of contractile proteins and of reparative growth (5) will lead to a gradual decline of contractile properties of the heart.

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Authors and Affiliations

  1. Radiobiological Institute TNO-Rijswijk, the Netherlands

    W. A. R. van Heeswijk, T. Stoffer, M. J. D. Eenink, W. Potman & J. Feijen

  2. Dept. of Chem. Technology, Twente University of Technology, Enschede, Netherlands

    W. J. F. van der Vijgh, J. v.d. Poort & H. M. Pinedo

  3. Dept. of Internal Medicine, Free University Hospital, Amsterdam, Netherlands

    P. Lelieveld

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  1. W. A. R. van Heeswijk
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  3. M. J. D. Eenink
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Editors and Affiliations

  1. Case Western Reserve University, Cleveland, Ohio, USA

    James M. Anderson

  2. University of Utah, Salt Lake City, Utah, USA

    Sung Wan Kim

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© 1984 Springer-Verlag US

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van Heeswijk, W.A.R. et al. (1984). Synthesis, Characterization and Antitumor Activity of Macromolecular Prodrugs of Adriamycin. In: Anderson, J.M., Kim, S.W. (eds) Recent Advances in Drug Delivery Systems. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2745-5_6

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  • DOI: https://doi.org/10.1007/978-1-4613-2745-5_6

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