Immobilized liposome layers for drug delivery applications: inhibition of angiogenesis.
Liposomes were immobilized onto the surface of perfluorinated polymer tape samples and tissue culture polystyrene well-plates using a multilayer immobilization strategy. In the first step, a thin interfacial bonding layer with surface aldehyde groups was deposited from a glow discharge struck in acetaldehyde vapour. Polyethylenimine was then covalently bound onto the aldehyde groups by reductive amination, followed by covalent binding of NHS-PEG-biotin molecules onto the surface amine groups by carbodiimide chemistry. Next, NeutrAvidin protein molecules were bound onto the PEG-biotin layer. Finally, liposomes containing PEG-biotinylated lipids were docked onto the remaining binding sites of the surface-immobilized NeutrAvidin molecules. AFM was used to image surface-bound liposomes and revealed a density well below close packing. The release characteristics of the surface-bound liposomes were measured by the fluorescence intensity changes of carboxyfluorescein upon release. Liposomes filled with sodium orthovanadate were surface immobilized and used in two in vitro angiogenesis assays. Marked differences compared to various control samples were observed, demonstrating the utility of drug-filled, surface-bound liposomes for evoking localized, controlled biological host responses proximal to an implanted biomedical device.
Vermette
Patrick
P
CSIRO Molecular Science, Bag 10, Clayton South, Victoria 3169, Australia. patrick.vermette@courrier.usherb.ca
Meagher
Laurence
L
Gagnon
Edith
E
Griesser
Hans J
HJ
Doillon
Charles J
CJ
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D051381:Rats
D020533:Angiogenesis Inhibitors; D008081:Liposomes