Mechanistic Study on Toxicity of Positively Charged Liposomes Containing Stearylamine to Blood

Abstract

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.