title: Antitumor activity of mannan-methotrexate conjugate in vitro and in vivo.
abstract: 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.
authors: Laboratory of Biomedical Chemistry, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
authors: Renata
authors: R
authors: Budzynska
authors: Dmitry
authors: D
authors: Nevozhay
authors: Urszula
authors: U
authors: Kanska
authors: Monika
authors: M
authors: Jagiello
authors: Adam
authors: A
authors: Opolski
authors: Joanna
authors: J
authors: Wietrzyk
authors: Janusz
authors: J
authors: Boratynski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008351:Mannans / Q000494:pharmacology*; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008351:Mannans; D008727:Methotrexate