Mechanistic study on toxicity of positively charged liposomes containing stearylamine to blood.
We studied the interaction of stearylamine (SA) containing liposomes (SA-liposomes) with erythrocyte ghost (EG) or platelets, utilizing the Tb/dipicolinate (Tb/DPA) assay for the mixing of aqueous contents and a resonance energy transfer (RET) assay for the mixing of lipid. The results demonstrate that SA-liposomes and EG, after aggregation, have a great tendency to mix their lipid before the mixing of the internal contents. The mixing of their contents takes place inside the vesicles due to the fusion of SA-liposomes and EG, followed by the leakage of the contents from the vesicles. In the presence of carboxymethyl chitin (CM-chitin), SA-liposomes-EG interaction was inhibited, indicating that CM-chitin reduces the tendency of SA-liposomes to interact with EG. The lipid mixing between SA-liposomes and platelets was not affected by CM-chitin or phagocytosis inhibitors: EDTA, cytochalasin B, or 2,4-dinitrophenol and iodoacetate, indicating the importance of glycoproteins on the platelet membrane surface in the interaction of SA-liposomes with platelets.
Nishiya
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Artificial Cells & Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Lam
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RT
Eng
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Zerey
M
M
Lau
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S
D000588:Amines / Q000633:toxicity*; D001792:Blood Platelets / Q000187:drug effects*; D002412:Cations; D004735:Energy Transfer; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D008563:Membrane Lipids / Q000633:toxicity*; D013050:Spectrometry, Fluorescence
D000588:Amines; D002412:Cations; D008081:Liposomes; D008563:Membrane Lipids; C009317:stearylamine