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 multipledose
schedule, when the advantage of T40-MTX over T10-MTX
was cumulative during the prolonged course of administration. |
