Polyelectrolyte Multilayers Promote Stent-MediatedDelivery of DNA to Vascular Tissue.

Wereport an approach to deliver DNA to vascular tissue in vivousing intravascular stents coated with degradable,DNA-containing polyelectrolyte multilayers (PEMs). Ionically cross-linkedmultilayers ∼120 nm thick were fabricated layer-by-layer onthe surfaces of balloon-mounted stainless steel stents using plasmidDNA and a hydrolytically degradable poly(β-amino ester) (polymer 1). Characterization of stents coated using a fluorescentlyend-labeled analog of polymer 1revealed film erosionto be uniform across the surfaces of the stents; differential stressesexperienced upon balloon expansion did not lead to faster film erosionor dose dumping of DNA in areas near stent joints when stents wereincubated in physiologically relevant media. The ability of film-coatedstents to transfer DNA and transfect arterial tissue in vivowas then investigated in pigs and rabbits. Stents coated with filmsfabricated using fluorescently labeled DNA resulted in uniform transferof DNA to sub-endothelial tissue in the arteries of pigs in patternscorresponding to the locations and geometries of stent struts. Stentscoated with films fabricated using polymer 1and plasmidDNA encoding EGFP resulted in expression of EGFP in the medial layersof stented tissue in both pigs and rabbits two days after implantation.The results of this study, combined with the modular and versatilenature of layer-by-layer assembly, provide a polymer-based platformthat is well suited for fundamental studies of stent-mediated genetransfer. With further development, this approach could also proveuseful for the design of nonviral, gene-based approaches for preventionof complications that arise from the implantation of stents and otherimplantable interventional devices. [ABSTRACT FROM AUTHOR]