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Synthesis and Biological Evaluation of Peg-Substituted Macromolecular Prodrugs of Mitomycin C

Polymer Materials Research Group, University of Ghent, Krijgslaan 281 9000 Gent, Belgium

E. Schacht

Polymer Materials Research Group, University of Ghent, Krijgslaan 281 9000 Gent, Belgium; Institute Biomedical Technology, University of Ghent (IBITECH)etienne.schacht{at}rug.ac.be

B. Rihova

Institute of Microbiology, Academy of Sciences of the Czech Republic Videnska 1083, 142 20 Prague 4

Poly(ethylene glycol) (PEG)-substituted macromolecular mitomycin C (MMC)-derivatives were synthetized using poly[N⁵-(2-hydroxyethyl)-L-glutamine] as the polymeric backbone. As an oligopeptide spacer between the drug and the polymer, tetrapeptide gly-phe-ala-leu was selected. To study the influence of PEG side groups on the antitumor activity of the derivatives, the conjugates were evaluated biologically in vitro and in vivo. The in vitro experiments showed only a minor influence of the PEGside groups on the antitumor activity. The results of the in vivo experiments on mice with a human type tumor were promising. Some derivatives lead to a remarkable tumor size regression. Furthermore, in vivo treatment of tumor bearing mice with the macromolecular MMC derivatives resulted in significantly longer survival times compared to free MMC.

Journal of Bioactive and Compatible Polymers, Vol. 17, No. 2, 123-138 (2002)
DOI: 10.1106/088391102024443


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