Effects of cis-diamminedichloroplatinum (II) loaded liposomes on mouse Ehrlich tumor cells

Cis-diamminedichloroplatinum II (cisplatin) heavily or lightly loaded (fluid, solid, negatively charged or neutral) liposomes were prepared. Cisplatin release from liposomes was observed only after long dialysis times or after liver lysosomal enzymatic disintegration in solution. Mouse Ehrlich tumor cells (ELT) cultured in vitro were treated with cisplatin, liposomes or cisplatin loaded liposomes, and the effects on the mitotic activity, the DNA content and the ultrastructure were compared. Cisplatin (1-10 micrograms/ml) had an antimitotic activity and modified the DNA content in ELT cells. Ribosome aggregation, perichromatin or interchromatin granule accumulation, and chromatin condensation or some degree of dispersion could be observed. Negatively charged fluid liposomes had an antimitotic activity and modified the DNA content in ELT cells at lower concentrations (0.3 mumoles/ml) than in the case of neutral fluid liposomes (1.5 mumoles/ml). Negatively charged solid liposomes were not toxic at these concentrations. Ultrastructural analysis of ELT cells treated in vitro with negatively charged fluid liposomes revealed their extracellular adsorption and their disintegration in phagolysosomes. A fusion between liposomes and the plasma membrane was not definitely demonstrated. Cisplatin loaded liposomes also had an antimitotic activity and modified the DNA content in ELT cells. These effects were similar to or more pronounced than those induced by free cisplatin. Ultrastructural analysis revealed some kind of electron dense material in phagolysosomes which was never observed after the treatment with free cisplatin or liposomes alone. Effects on nucleic acids were rarely observed.