Toxicity of gamma irradiated liposomes. 1. In vitro interactions with blood components

Gamma irradiation is a potential technique for sterilisation of liposome su spensions. Unfortunately, gamma irradiation may result in chemical degradat ion of the phospholipids and the toxicological aspects have to be considere d. The effects of liposome composition and gamma irradiation on the interac tions of the liposomes with the hemostatic mechanisms (hemolysis, aggregati on and coagulation) were studied. Non-irradiated liposome suspensions showe d no hemolysis of erythrocytes. After irradiation, up to 3.1% hemolysis was measured. Least hemolysis was observed with irradiated liposomes composed of unsaturated or charged phospholipids. The negatively charged DSPG-liposo mes (both non-irradiated and irradiated) induced aggregation of platelets a s observed by the spectrophotometric method. However, no aggregates were se en in the microscope or measured by the aggregometer. Negatively charged li posomes also affected the coagulation cascade where prolonged coagulation t imes were measured. Irradiation of the liposome suspensions resulted in eve n longer coagulation times. The prolonged coagulation times correlated to s ome extent with the measured binding and depletion of calcium from plasma b y the negatively charged liposomes. (C) 1999 Elsevier Science B.V. All righ ts reserved.