Synthesis and biological activity of the functional block-copolymers basedon pluronic P85-doxorubicin conjugates

Two types of the conjugate of ethylene oxide (A)- propylene oxide (B) block copolymer (ABA type, pluronic P85) with the antitumor antibiotic doxorubic in were synthesized. Conjugate K1 was obtained by acylating the amino group s of doxorubicin with N-hydroxysuccinimide ester of pluronic P85 hemisuccin ate. Conjugate K2 was synthesized by alkylating the amino group of the drug with a bromoacetyl residue attached to the pluronic. The cytotoxicity of t he K1ad K2 conjugates was studied on the human ovary carcinoma cell culture s SKOV3 and SKVLB. The SKOV3 cell line is sensitive to doxorubicin, and the SKVLB is a multi-drug-resistant derivative of the former line, with the ce ll surface containing a gP-170 protein effectively eliminating drugs from t he cell, it was found that the K1 conjugate possesses a much lower cytotoxi city with respect to the cells of both types as compared to the free doxoru bicin. At the same time, K2 showed a much more pronounced cytotoxicity than the free antibiotic toward stable cells, while its activity toward sensiti ve cells was comparable to that of the free drug. Experiments on mice of th e BALB/c line showed extremely low general toxicity of the K2 conjugate. Th ese results show good prospects for using K2 in the therapy of multi-drug-r esistant tumors.