1 research outputs found
Polyelectrolyte Multilayers Promote Stent-Mediated Delivery of DNA to Vascular Tissue
We
report an approach to deliver DNA to vascular tissue <i>in vivo</i> using intravascular stents coated with degradable,
DNA-containing polyelectrolyte multilayers (PEMs). Ionically cross-linked
multilayers ∼120 nm thick were fabricated layer-by-layer on
the surfaces of balloon-mounted stainless steel stents using plasmid
DNA and a hydrolytically degradable polyÂ(β-amino ester) (polymer <b>1</b>). Characterization of stents coated using a fluorescently
end-labeled analog of polymer <b>1</b> revealed film erosion
to be uniform across the surfaces of the stents; differential stresses
experienced upon balloon expansion did not lead to faster film erosion
or dose dumping of DNA in areas near stent joints when stents were
incubated in physiologically relevant media. The ability of film-coated
stents to transfer DNA and transfect arterial tissue <i>in vivo</i> was then investigated in pigs and rabbits. Stents coated with films
fabricated using fluorescently labeled DNA resulted in uniform transfer
of DNA to sub-endothelial tissue in the arteries of pigs in patterns
corresponding to the locations and geometries of stent struts. Stents
coated with films fabricated using polymer <b>1</b> and plasmid
DNA encoding EGFP resulted in expression of EGFP in the medial layers
of stented tissue in both pigs and rabbits two days after implantation.
The results of this study, combined with the modular and versatile
nature of layer-by-layer assembly, provide a polymer-based platform
that is well suited for fundamental studies of stent-mediated gene
transfer. With further development, this approach could also prove
useful for the design of nonviral, gene-based approaches for prevention
of complications that arise from the implantation of stents and other
implantable interventional devices