Liposomes coated with chemically modified dextran interact with human endothelial cells

Some Liposomal formulations are now in clinical use. New applications in bi ology and medicine using targeted liposomes remain an intensive research ar ea. Ln this context, liposomes constituted of phosphatidylcholine (PC), pho sphatidylethanolamine (PE), and cholesterol (70/10/20 mol %) were prepared by detergent dialysis and coated with dextran (Dx) or functionalized dextra n (FDx), both hydrophobized by a cholesterol anchor which penetrates the li pid bilayer during the vesicle formation. The coating of liposomes with the se polysaccharides was performed because chemically modified dextran but no t native Dr interacted with vascular cells. The liposome uptake by human en dothelial cells was followed using uncoated and coated Liposomes radiolabel ed with a neutral Lipid (H-3-cholesterol) and a polar phospholipid (C-14-PC ). The results indicated for both radiolabels a preferential uptake by endo thelial cells of FDx-coated liposomes compared to uncoated or Dr-coated lip osomes. Addition to the culture medium of calcium up to 10 mM further enhan ced the level and rate of incorporation of FDx-coated liposomes, whereas in teraction of endothelial cells with uncoated liposomes or liposomes coated with Dr was poorly affected. Liposome membranes were then labeled with N-(l issamine rhodamine B sulfonyl)diacyl-PE and liposome uptake by endothelial cells was observed by fluorescence microscopy. The punctate intracellular f luorescence 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 cultu re. Consequently, these liposomes coated with bioactive polymers represent an attractive approach as materials for use as drug delivery vehicles targe ting vascular cells. (C) 1999 John Wiley & Sons, inc.