Background: The search for new, innovative methods to treat all types of diseases, especially cancer-related
ones, is a challenge taken by pharmaceutical companies and academic institutions. The use of conjugates
containing widely-known and widely-used bioactive substances is one of the ways to solve this problem.
Research into drug binding with macromolecular carrier systems has joined the search for new therapeutic
strategies.
Methods: The main goal of this paper is the potential offered by the use of fibrinogen derivatives as an antileukemic
drug carrier. Physicochemical properties of the obtained conjugate were analyzed, characterizing
alterations in relation to the starting carrier and analyzing biological implications. The intraperitoneally
(i.p.) inoculated P388 mouse leukemia model for in vivo studies was used.
Results and conclusions: Conjugates consisting of a fibrinogen derivative with a covalently bound anticancer
drug were developed. Carrier preparation and a conjugate synthesis in aqueous solution were formulated,
as well as purification of the conjugate was performed. The study showed that the survival of leukemia
mice treated with FH–MTX conjugate was indeed significantly longer than survival in both untreated animals
(control) and mice treated with unbound MTX. A significant increase in the antileukemic activity of MTX conjugated
with hydrolysed fibrinogen was observed as compared with the unconjugated drug. Reported data
suggest that hydrolysed fibrinogen can serve as a carrier molecule for the MTX drug with the aim of enhancing
its antileukemic activity.
General significance: Conjugates consisting of a fibrinogen derivative with a covalently bound anticancer drug
seem to be a promising anticancer drug. |
