Interactions of functionalized dextran-coated liposomes with vascular smooth muscle cells.
Synthetic polymers are commonly used in the medical field as implants, polymeric drugs, or drug delivery systems. Among them, bioactive sulfated polysaccharides such as chemically modified dextrans are described to exhibit various properties including the inhibition of smooth muscle cell (SMC) growth. SMCs are key cellular components involved in the physiopathology of the vascular walls especially in atherosclerosis or after vascular surgeries. Interestingly, binding sites on vascular SMCs were already observed for an antiproliferative functionalized dextran (FDx). In this context, we hypothesized that this bioactive polymer could be used as a targeting moiety on the surface of drug delivery systems. In this work, liposomes constituted of phosphatidylcholine, phosphatidylethanolamine and cholesterol (70/10/20 mol.%) were prepared and coated with FDx hydrophobized by a cholesterol anchor (CholFDx) which penetrates the lipid bilayer during the liposome formation. The liposome interactions with SMCs were then followed using radiolabeled liposomes and fluorolabeled liposomes. Results of radioactivity on SMCs indicated higher interactions with CholFDx-coated liposomes as compared to uncoated liposomes. The fluorescence of cells incubated with fluorolabeled CholFDx-coated liposomes also evidenced the liposome binding on SMC membranes. These data demonstrated that liposomes coated with FDx interacted with vascular SMCs. Consequently, the coating with such bioactive polymers appears promising for the design of new drug delivery systems for the targeting of vascular cells.
Letourneur
D
D
LRM, CNRS UMR 7540, Institut Galilée, University Paris 13, Av. J.B. Clément, 93 430, Villetaneuse, France. letourne@galilee.univ-paris13.fr
Parisel
C
C
Prigent-Richard
S
S
Cansell
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002118:Calcium / Q000737:chemistry; D002478:Cells, Cultured; D002784:Cholesterol; D003911:Dextrans / Q000378:metabolism*; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D010713:Phosphatidylcholines; D051381:Rats; D017207:Rats, Sprague-Dawley
D003911:Dextrans; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D002118:Calcium