Background: The aim of the study was to compare
the antileukemic activity of methotrexate (MTX) conjugates with
native and glycated fibrinogen. We expected that conjugates
based on glycated fibrinogen would reveal higher antileukemic
activity because of decreased plasmin digestibility and a higher
retention rate of glycated fibrinogen in the body. Materials and
Methods: Fibrinogen was glycated using a high-temperature
procedure at 65-85ÆC. Glycated fibrinogens were examined with
respect to their ability to clot and susceptibility to plasmin
digestion. Native fibrinogen (F) and fibrinogens glycated at 65
and 73ÆC (F65 and F73) were conjugated with MTX and tested
in mice bearing P388 leukemia, at a dose of 40 mg of MTX per
kg of body weight. Results: Glycated fibrinogens retained their
ability to clot. Compared to native fibrinogen, they were more
resistant to digestion by plasmin. All tested conjugates revealed
higher antitumor activity than the free drug. Increases in average
lifespan over the control group were 34% for free MTX, 137%
for F-MTX, 151% for F65-MTX and 91% for F73-MTX. The
differences between the antitumor activities of all conjugates
were not statistically significant. Conclusion: It seems necessary
to compare the antitumor activities of MTX conjugates based
on native and glycated fibrinogen in different tumor models, to
demonstrate the expected differences. |
