title: The effect of the substitution level of some dextran-methotrexate conjugates on their antitumor activity in experimental cancer models.
abstract: Methotrexate (MTX) is widely used in the treatment of a number of oncological and hematological diseases. Due to its known limitations, MTX is often conjugated with different carriers to obtain amended forms of the drug. In this study, the potential influence of the substitution level (loading ratio) of the dextran T10- and T40-based MTX conjugates (D-MTX) on their properties were investigated in vitro and in vivo. The clear dependence of the in vitro antiproliferative effect on the substitution level was established only in the case of the dextran T10-based preparations (T10-MTX conjugates). Conjugates with the higher substitution level had the lower antiproliferative effect. For the dextran T40-based (T40-MTX conjugates) set no similar relationship was observed in the tested range of substitution levels, nor was any dependence observed between the biological properties of the D-MTX preparations in vivo and their substitution levels. However, the difference between the two conjugates was well pronounced in a multiple-dose schedule, when the advantage of T40-MTX over T10-MTX was cumulative during the prolonged course of administration.
authors.affiliation: Laboratories of Experimental Anticancer Therapy, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla st., 12, 53-114 Wroclaw, Poland.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Nevozhay
authors.forename: Renata
authors.initials: R
authors.lastname: Budzynska
authors.forename: Monika
authors.initials: M
authors.lastname: Jagiello
authors.forename: Urszula
authors.initials: U
authors.lastname: Kanska
authors.forename: Mohamed Salah
authors.initials: MS
authors.lastname: Omar
authors.forename: Adam
authors.initials: A
authors.lastname: Opolski
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Janusz
authors.initials: J
authors.lastname: Boratynski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D000964:Antimetabolites, Antineoplastic; D003911:Dextrans; D004337:Drug Carriers; D008727:Methotrexate