Liposomes coated with chemically modified dextran interact with human endothelial cells.
Some liposomal formulations are now in clinical use. New applications in biology and medicine using targeted liposomes remain an intensive research area. In this context, liposomes constituted of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cholesterol (70/10/20 mol %) were prepared by detergent dialysis and coated with dextran (Dx) or functionalized dextran (FDx), both hydrophobized by a cholesterol anchor which penetrates the lipid bilayer during the vesicle formation. The coating of liposomes with these polysaccharides was performed because chemically modified dextran but not native Dx interacted with vascular cells. The liposome uptake by human endothelial cells was followed using uncoated and coated liposomes radiolabeled with a neutral lipid (3H-cholesterol) and a polar phospholipid (14C-PC). The results indicated for both radiolabels a preferential uptake by endothelial cells of FDx-coated liposomes compared to uncoated or Dx-coated liposomes. Addition to the culture medium of calcium up to 10 mM further enhanced the level and rate of incorporation of FDx-coated liposomes, whereas interaction of endothelial cells with uncoated liposomes or liposomes coated with Dx was poorly affected. Liposome membranes were then labeled with N-(lissamine rhodamine B sulfonyl)diacyl-PE and liposome uptake by endothelial cells was observed by fluorescence microscopy. The punctate intracellular fluorescence of cells incubated at 37 degrees C with fluorolabeled liposomes is indicative of the liposome localization within the endocytotic pathway of the cells. Altogether, these data demonstrate that coating of liposomes with FDx enable specific interactions with human endothelial cells in culture. Consequently, these liposomes coated with bioactive polymers represent an attractive approach as materials for use as drug delivery vehicles targeting vascular cells.
LRM, CNRS UMR 7540, Institut Galilée, University Paris XIII, Av. J. B. Clément, 93430 Villetaneuse, France.
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Cansell
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Parisel
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Jozefonvicz
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Letourneur
D001672:Biocompatible Materials / Q000737:chemistry; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D008081:Liposomes; D008422:Materials Testing; D013499:Surface Properties
D001672:Biocompatible Materials; D003911:Dextrans; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D002118:Calcium