POTENTIATION OF RICIN CYTOTOXICITY BY LIPOSOMAL MONENSIN UNDER IN-VITRO AND IN-VIVO CONDITIONS

Effect of monensin, intercalated in liposomes on the cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in phagocytic and nun-phagocytic cells as well as in mice has been studied: Intercalatio n does not disturb the integrity of the liposomal bilayer and substant ially enhances the cytotoxicities of ricin and Pseudomonas exotoxin A in both phagocytic and non-phagocytic cells while it has no effect on diptheria toxin. The observed effect is highly dependent on the liposo mal lipid composition as well as cell types. The potentiating ability of monensin in neutral vesicle is 2.2-fold higher, than in negatively charged vesicles in non-phagocytic cells while no difference was obser ved in phagocytic cells. Incorporation of stearylamine in liposemes re duces the potentiating effect of monensin. Liposomal monensin has also been found to enhance the cytotoxicity of ricin in mouse in vivo in a dose-dependent manner and is maximal when ricin is injected within 60 min of monensin injection. Liposomal monensin remains in circulation for 2 hr while free monensin remains only for 15 min. Tissue distribut ion studies reveal that liposomal monensin is present mainly in the li ver and spleen which are also the major sites for ricin accumulation. Thus liposome is found to be an effective delivery vehicle for monensi n to potentiate the cytotoxicity of immunotoxins or hormono-toxins and could prove useful for selective elimination of cancer cells.