Effect of Polycation Complexation on Methotrexate-Liposome Cytotoxicity

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Abstract
Methotrexate and methotrexate-DEAE dextran complex were microencapsulated in positively charged liposomes. Their cytotoxicity was determined and compared with the cytotoxicity of control systems against L1210 mouse leukemia eel Is at 37°C In acetate buffer of pH 7.40 ± 0.05. The control systems used were acetate buffer, blank liposome, DEAE-dextran liposome and methotrexate solution. The methotrexate and methotrexate-DEAE dextran liposomes were lyophilized and the Influence of lyophilization on their cytotoxicity was also examined. The methotrexate-DEAE dextran liposomes resulted in slightly higher mean growth ratios than the free methotrexate liposomes in non lyophilized as well as lyophilized systems. The ED50 values for methotrexate and methotrexate-DEAE dextran liposomes were similar to that for the free methotrexate solution. This observation indicated that microencapsulation of methotrexate in liposomes either as a free drug or a complex has no effect on the cytotoxicity of the drug. In addition, lyophilization of liposome products does not seem to change their effectiveness.