Interaction of cisplatin with planar model membranes - dose dependent change in electrical characteristics

The drug cisplatin has broad antineoplastic activity against advanced testicular and ovarian cancers, epithelial malignancies, cancers of the head, neck, bladder, oesophagus and lungs. Peripheral neurotoxicity, ototoxicity and nephrotoxicity are its major side effects. The nonspecific action of this drug on the lipid bilayer architecture of membranes has been studied by following the effects produced on the electrical characteristics of model planar bilayer lipid membranes (BLM). The results confirm that the drug has a strong surface interaction with the zwitterionic polar head groups of the amphipathic phospholipids constituting the BLM. The permeability characteristics of cisplatin through the hydrophobic core are limited. Cisplatin does not fluidise the membrane sufficiently to cause its breakdown but creates small ion conducting defects on the membrane bilayer resulting in a marginal increase in ion conductivity. These results indicate that cisplatin exhibits a non-specific action on the lipid bilayer component of the membrane which might be partly responsible for its neurotoxic side effects.