Release of Plasmid DNA from Intravascular Stents Coated with Ultrathin Multilayered Polyelectrolyte Films

Abstract

Materials that permit control over the release of DNA from the surfaces of topologically complex implantable devices, such as intravascular stents, could contribute to the development of new approaches to the localized delivery of DNA. We report the fabrication of ultrathin, multilayered polyelectrolyte films that permit both the immobilization and controlled release of plasmid DNA from the surfaces of stainless steel intravascular stents. Our approach makes use of an aqueous-based, layer-by-layer method for the assembly of nanostructured thin films consisting of alternating layers of plasmid DNA and a hydrolytically degradable polyamine. Characterization of coated stents using scanning electron microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin film ca. 120 nm thick that adhered conformally to the surfaces of stent struts. These ultrathin films did not crack, peel, or delaminate substantially from the surface after exposure to a range of mechanical challenges representative of those encountered during stent deployment (e.g., balloon expansion). Stents coated with eight bilayers of degradable polyamine and a plasmid encoding enhanced green fluorescent protein sustained the release of DNA into solution for up to four days when incubated in phosphate buffered saline at 37 °C, and coated stents were capable of mediating the expression of EGFP in a mammalian cell line without the aid of additional transfection agents. The approach reported here could, with further development, contribute to the development of localized gene-based approaches to the treatment of cardiovascular diseases or related conditions.

Matrices and scaffolds for DNA delivery in tissue engineering

“…More recently, vectors have been immobilized in layers on surfaces using a technique termed polyelectrolyte layering [113][114][115][116]. Nanoscale films are created with alternating layers of negatively charged plasmid and positively charged polymers that are deposited on materials such as stainless steel stents [113][114][115][116].…”

“…Nanoscale films are created with alternating layers of negatively charged plasmid and positively charged polymers that are deposited on materials such as stainless steel stents [113][114][115][116]. The duration of plasmid release can be manipulated through changing the degradability, conductivity, or electrochemistry of the polymer layers or substrate, while the released DNA is able to transfect cells without the aid of additional transfection agents [114,115]. Multilayered polyelectrolyte films have the ability to create highly tunable surfaces, and with the appropriate design of each layer, may potentially enable the sequential release of multiple gene sequences.…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…Thus, several degradable multilayers of bio-polyelectrolytes, such as polysaccharides, polypeptides or polynucleotides have been reported by Picart et al [292]. Lynn et al [293][294][295][296][297][298][299][300][301] introduced poly α,β-aminoesters for the fabrication of capsules with degradable multilayers. Harashima et al [302] reported multifunctional envelope-type-nanocapsules including a nucleic acid core complex with polycations or lipid aggregates and also different polymeric shell structures equipped with specific functional groups binding ligand-targeted agents and cell-penetrating proteins.…”

Ultrathin Multilayered Films that Promote the Release of Two DNA Constructs with Separate and Distinct Release Profiles

“…[7][8][9][10] These methods are entirely aqueous and permit nanometer-scale control over the structures of thin films fabricated from a wide variety of synthetic or natural polyelectrolytes, [7][8][9][10] [16][17][18][19][20] have demonstrated that it is possible to design multilayers that release DNA and promote surface-mediated cell transfection by fabricating films using DNA and cationic polymers that are hydrolytically, [12][13][14][15] enzymatically, [16,17] or reductively [18,19] degradable. Approaches to the fabrication, characterization, and application of DNAcontaining multilayers have been reviewed recently.…”

“…[12][13][14] For these and all other experiments described below, films were fabricated on planar silicon substrates to permit characterization of film growth and erosion using ellipsometry. Figure 1 shows a plot of optical film thickness versus the number of polyamine/DNA layers (referred to hereafter as 'bilayers') deposited for films fabricated using either polymers 2a-d or unsubstituted PAH.…”