HPMA Copolymer Conjugates of DOX and Mitomycin C for Combination Therapy: Physicochemical Characterization, Cytotoxic Effects, Combination Index Analysis, and Anti-Tumor Efficacy

The synthesis, characterization and results of evaluation of the biological behavior of HPMA copolymer conjugates bearing anti‐cancer drugs doxorubicin and mitomycin C are described. Two HPMA copolymer carrier types were synthesized: the linear copolymer and the biodegradable high‐molecular‐weight diblock copolymer containing a degradable disulfide bond. The polymer‐drug conjugates incubated in buffers modeling the intracellular environment released the drugs more rapidly than those incubated in bloodstream conditions. Significant in vitro and in vivo antitumor synergistic activity of the conjugates in the treatment of EL‐4 T‐cell demonstrates their high potential for solid tumor treatment. The synthesis and biological evaluation of linear or biodegradable diblock HPMA copolymer conjugates bearing two anti‐cancer drugs, doxorubicin and mitomycin C, attached via pH‐labile hydrazone bond are described. As in vivo therapeutic efficacy correlates with highest M‾w and the best combination index, it can be judged that the EPR effect and synergistic effect of drugs are co‐responsible for the final pharmacological effectiveness of the tested conjugates.