Toxicity of sphingomyelin-containing liposomes after chronic injection into mice.

Chronic treatment (10 i.p. injections over 20 days) of Balb/c mice with SM liposomes led to 50 and 300% enlargement of the liver and spleen respectively. No such effect was observed after similar treatment with PC liposomes. Biochemical analysis of the enlarged tissues showed no significant changes in the concentrations of glycolipid, phospholipid and certain hydrolytic enzymes. However, the increase in tissue size was paralleled by an increase in protein content. Light and electron microscopy studies of the enlarged tissues revealed an increase in the number of Kupffer cells and collections of inflammatory cells in the liver and widespread granulomatous inflammation in the spleen. We conclude that SM liposomes, although probably toxic for use as a drug carrier, may serve as a model agent in the study of tissue granulomatous inflammation.