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.
Nishiya
T
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Artificial Cells & Organs Research Centre, McGill University, Montreal, Quebec, Canada.
Chang
T M
TM
D001769:Blood / Q000187:drug effects; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry / Q000633:toxicity*; D008561:Membrane Fusion / Q000187:drug effects; D010713:Phosphatidylcholines / Q000737:chemistry / Q000633:toxicity*; D010949:Plasma / Q000187:drug effects; D013816:Thermodynamics
D001802:Blood Substitutes; D008081:Liposomes; D010713:Phosphatidylcholines; D002686:Chitin; C044872:O-(carboxymethyl)chitin