Toxicity of liposomes containing low mol% of dienoyl phosphocholine to blood: use of carboxymethyl chitin to reduce toxicity.

Toxic effects of liposomes composed of the synthetic lipid, 1,2-bis(octadeca-2,4-dienoyl)-sn-glycero-3-phosphocholine (C18DENPC) and cholesterol (Cho) were studied. In the present work, we have explored, 1) fusion between C18DENPC/Cho-liposomes and erythrocyte ghost (EG) membranes with resonance energy transfer assay, 2) hemolysis induced by C18DENPC/Cho-liposomes and 3) turbidity changes in native plasma on contact with C18DENPC/Cho-liposomes, in the presence or absence of carboxymethyl chitin (CM-chitin). In the absence of CM-chitin, extents of fusion, hemolysis and turbidity changes in native plasma increased with the decrease in C18DENPC content. In the presence of CM-chitin at a concentration of 10(-3) or 10(-2)% (w/v), fusion of C18DENPC/Cho-liposome with EG was inhibited. Extents of hemolysis and turbidity changes in native plasma induced by C18DENPC/Cho-liposomes were reduced depending upon CM chitin concentration.