(532f) Release of DNA from Intravascular Stents Coated with Ultrathin Multilayered Polyelectrolyte Films

We report a layer-by-layer approach to the fabrication of ultrathin multilayered films that permits the immobilization and controlled release of plasmid DNA from the surfaces of stainless steel intravascular stents. Past studies demonstrating the release of DNA from stent surfaces have focused largely on the encapsulation of DNA in relatively thick (micrometer-scale) films of degradable polymers using methods that require the use of organic solvents. Our approach makes use of an entirely aqueous-based, layer-by-layer method for the assembly of ultrathin polyelectrolyte films fabricated from alternating layers of plasmid DNA and hydrolytically degradable polyamines. We sought to determine whether these methods could be used to fabricate assemblies on the surfaces of intravascular stents and, subsequently, whether these ultrathin films could withstand the range of mechanical forces typically associated with stent deployment. Characterization by scanning electron microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin film ca. 100 to 130 nm thick that adhered conformally to stent surfaces and struts. These ultrathin films did not crack, peel, or delaminate substantially from the surface after exposure to a range of physical challenges representative of those encountered during stent deployment (e.g., balloon expansion). Expanded stents coated with eight alternating layers of degradable polyamine and a plasmid construct (pEGFP-N1) encoding enhanced green fluorescent protein (EGFP) sustained the release of DNA for up to 2.5 days when incubated in phosphate buffered saline at 37 °C. The absolute amounts of DNA released could be tailored by controlling the numbers of layers of DNA deposited during fabrication. Finally, we have conducted cell-based experiments to demonstrate the ability of stents coated with these ultrathin materials to mediate the transfection of mammalian cells. The ultrathin films reported here could, with further development, contribute to the development of localized gene-based approaches to the treatment of cardiovascular diseases or the prevention of complications that arise from interventional procedures.