The interaction of liposomes with cells: The relation of cell specific toxicity to lipid composition

Abstract

Liposomes, which have been proposed as agent carriers, can themselves produce a wide variety of effects on the viability of co-incubated cells. In this study we show that the lipid composition of empty liposomes produced varied effects on the viability, as measured by [ 3 H]-thymidine incorporation, of leukemic cells and fibroblasts. Certain liposomal compositions, particularly those involving stearylamine, were highly toxic to both cell types. It is evident from this investigation that caution must be exercised in the choice of lipid composition if the effect of the liposomes is not to conceal that of the drug, or carried agent, either on the target cells in terms of therapeutic effect, or on normal cells in terms of toxicity. Normal lysophosphatides, having an acyl bond in sn-1, can be metabolised by both normal and leukemic cells; however the replacement of the acyl by an alkyl bond in a lysophosphatide requires an O-alkyl cleavage enzyme to be metabolised. Such an enzyme is present in a multifunctional oxygenase in normal cells but appears to be absent or inoperative in certain tumor cells. Coincubation of alkyl lysophosphatide containing liposomes is shown to produce selective destruction of L 1210 leukemic cells; in addition the liposomal form of such analogs is suggested as being more effective against leukemic cells and less toxic to normal cells than when used in the free form.