Aging of soya-PC liposomes containing vitamin E reverses the stimulating effects of freshly prepared liposomes on growth of fibroblasts in culture

Extruded soya-PC liposomes (VET) averaging 80.4 +/- 24.3 nm in diameter and containing 0 to 25% vitamin E were added to human fibroblasts in culture immediately after preparation or after a 4 month cold storage period (aged liposomes), Following 8 days of incubation, the effect on the growth, membrane permeability, and protein content of the fibroblasts was determined, The freshly prepared liposomes induced a proliferative effect on cell growth at low phospholipid concentrations (10 and 50 mu M). This effect was lost as the phospholipid concentration increased, and at concentrations exceeding 100 mu M the toxic effects of liposomes became apparent. The incorporation of vitamin E into the liposomes reduced this toxicity, Aged liposomes showed a loss of proliferative activity at phospholipid levels of 10 and 50 mu M. The age of the liposomes also influenced the protective effect of vitamin E on the cultures, Liposomes containing the vitamin and stored prior to use showed no proliferative effect, and cell toxicity increased with the percentage of vitamin initially present in the liposomes, The results suggest that vitamin E, incorporated into freshly prepared liposomes, is able to protect fibroblasts in culture from the toxic effects shown by phospholipid concentrations above 100 mu M. This protective effect was lost when liposomes were stored prior to use.