Open AccessAntitumor Activity of Mannan–Methotrexate Conjugate In Vitro and In Vivo
Author(s) -
Renata Budzyńska,
Dmitry Nevozhay,
Urszula Kañska,
Monika Jagiello,
Adam Opolski,
Joanna Wietrzyk,
Janusz Boratyński
Publication year - 2007
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/000000007783980837
Subject(s) - methotrexate , conjugate , in vivo , pharmacology , mannan , in vitro , chemotherapy , therapeutic index , leukemia , medicine , chemistry , drug , immunology , biochemistry , biology , polysaccharide , mathematical analysis , mathematics , microbiology and biotechnology
Conjugation of anticancer drugs with different carriers has been extensively studied recently as a potential method of obtaining improved drug forms. The conjugation often results in the increase of the therapeutic effect, alteration of a toxicity profile, and/or selective targeting of therapeutic agent to the tissue of interest. We have synthesized mannan-methotrexate conjugate by means of methotrexate anhydride and studied its antitumor properties both in vitro and in vivo in comparison with free methotrexate. Mannan-methotrexate conjugate showed significantly improved antitumor activity compared to free methotrexate in the model of P388 mouse leukemia disseminated in the peritoneal cavity treated with intraperitoneally injected chemotherapy. Conversely, the antitumor effects of free methotrexate and mannan-methotrexate conjugate were comparable when leukemia was implanted subcutaneously and chemotherapy agents were administered intravenously. These results suggest that mannan-methotrexate conjugate should be further investigated as a potential therapeutic agent for intraperitoneally disseminated tumors.