Antitumor effect of new conjugates of anthracycline antibiotic carminomycin bound to chitosan

Abstract

The antileukemic activities of two conjugates of the anthracycline antibiotic carminomycin – CX1 and CX2, were investigated. The direct cytotoxic efficacies of the two conjugates and free carminomycin (C), were measured by an MTT-assay which provides excellent reproducibility and statistical significance. The treatment of HL-60 cells with the three compounds for 48 and 96 hours showed considerable sensitivity to the free carminimycin, as well as to its conjugates CX1 and CX2. The ascetic form of leukemia P388 and leukemia L1210 (transplantation dose of 1·106 tumor cells) in hybrid mice BDF1 was used as leukemic models. All compounds investigated showed a maximal cytotoxic response and strong concentration dependence. By comparing the cytotoxic profile of carminomycin to those of CX1 and CX2, it can be assumed that a slower release of the active drug carminomycin have occurred. The criterion T/C showed a considerable antileukemic effect from 1.0 to 18.0 mg/kg. In conclusion, the conjugates CX1 and CX2 represent biologically active compounds with a putative depot-effect of slow release of the active intercalating agent carminomycin.

Keywords

• carminomycin
• pharmacokinetics
• hl-60 cells
• leukemia p388
• leukemia l1210
• chitosan
• anthracycline antibiotics