Drug-eluting stent with improved durability and controllability properties, obtained via electrocoated adhesive promotion layer.

Drug-eluting stents (DES) have become an accepted technology in intravascular intervention. Manufacturing methodologies of DES are based mainly on mechanical processes, which tend to generate coatings that have poor stability properties; these were recently related as a potential hazard. A novel approach for significantly increasing the adhesion of polymer coatings onto DES is presented. The method is based on the electrochemistry of diazonium salts. These substances are organic compounds with the characteristic structure of R-N(2) (+) X(-), where R is an organic residue and X(-) is an anion. The objective of this article is to study the properties of a selected diazonium salt 4-(1-dodecyloxy)-phenyldiazonium tetrafluoroborate, referred as C(12)-phenyldiazonium. This material was found to be a superior adhesive promoter for polymeric coatings applied onto metallic stents. C(12)-phenyldiazonium was synthesized and electrocoated on metallic stents and plates. The multilayer films of C(12)-phenyldiazonium were further characterized through electrochemical (cyclic voltammetry, impedance spectroscopy), physical (light and scanning electron microscopy, X-ray photoelectron spectroscopy, peeling tests), and chemical methodology (high pressure liquid chromatography). Further biocompatibility properties of the electrocoated basecoat were evaluated using in vitro and in vivo models. Synthesized C(12)-phenyldiazonium was successfully electrocoated onto metallic surfaces. Electrochemical tests demonstrated its efficient and controllable electrocoating. C(12)-phenyldiazonium was found to increase polymeric coating stability as was reflected by a standard adhesion test. Electrocoated metallic stents spray-coated with a second polymeric film showed improved durability following incubation in physiological buffer. Furthermore, this improvement in durability exhibits stabilized drug release. In addition, biocompatibility evaluations have demonstrated basecoat's inert properties.

Evaluation of drug-eluting stents' coating durability--clinical and regulatory implications.

Drug-eluting stents (DES) revolutionized cardiovascular treatment by virtually eliminating in-stent restanosis. However, in the past 3 years the U.S. Food and Drug Administration and published studies have raised several safety issues regarding DES such as late state thrombosis and increased mortality. Recent publications have described DES coating delaminating, cracking, and peeling in commercially available stents. It has been suggested that these properties are responsible for the deleterious effects. The goal of this work is to describe a quantitative in vitro durability tests for DES, referred to as Quantified Defects (QD). The technique was implemented on various stent polymer-coated models to determine its ability to differentiate between coating properties. Stents' coating defects were tested using light microscopy, scanning electron microscopy, and a micro-balance. High-performance liquid chromatography was used for measuring drug release. Stents were incubated at either 37 or 60 degrees C and sampled at 0, 3, and 30 days. Stent coating durability was tested using stainless steel control stents versus stents having increased surface adhesion, both of which were then coated with conventional spray-coating methods. Drug-coated stents tested for defects demonstrated a deteriorating durability profile as reflected by QD indices. Different coating models showed unique QD indices that reflected their superior or inferior coating durability. These results indicated that the methodology was able to differentiate between different models. In conclusion, this simple low-cost testing methodology can be easily used during DES development, with either durable or biodegradable polymers.

Drug-eluting stents in preclinical studies: updated consensus recommendations for preclinical evaluation.

Coronary drug-eluting stents are commonplace in clinical practice with acceptable safety and efficacy. Preclinical evaluation of novel drug-eluting stent technologies has great importance for understanding safety and possibly efficacy of these technologies, and well-defined preclinical testing methods clearly benefit multiple communities within the developmental, testing, and clinical evaluation chain. An earlier consensus publication enjoyed widespread adoption but is in need of updating. This publication is an update, presenting an integrated view for testing drug-eluting technologies in preclinical models, including novel devices such as bioabsorbable coatings, totally bioabsorbable stents, bifurcation stents, and stent-free balloon-based drug delivery. This consensus document was produced by preclinical and translational scientists and investigators engaged in interventional technology community. The United States Food and Drug Administration (USFDA) recently issued a Draft Guidance for Industry Document for Drug-Eluting Stents. This expert consensus document is consistent with the Food and Drug Administration guidance. The dynamic nature of this field mandates future modifications and additions that will be added over time.

Regulatory approval of peripheral endovascular revascularization devices in the United States: is the horse still in the barn?

The regulatory processes by which industry obtains approval for marketing and sales of medical devices from the United States Food and Drug Administration is distinct from the drug approval pathways, poorly understood by clinicians, and widely criticized by clinical investigators and industrial sponsors of new technology. This paper reviews the most common pathways for obtaining such approval for endovascular devices used in the treatment of peripheral arterial disease. Unique issues pertinent to clinical trials carried out in this area are highlighted. Future directions for evolution of the regulatory process consonant with the mandated requirements for demonstration of safety and efficacy are discussed.

Dosimetry study of Re-188 liquid balloon for intravascular brachytherapy using polymer gel dosimeters and laser-beam optical CT scanner.

Angioplasty balloons inflated with a solution of the beta-emitter Re-188 have been used for intravascular brachytherapy to prevent restenosis. Coronary stents are in extensive clinical use for the treatment of de novo atherosclerotic stenoses. In this study, the effect of an interposed stent on the dose distribution has been measured for Re-188 balloon sources using the proprietary BANG polymer gel dosimeters and He-Ne laser-beam optical CT scanner. In polymer gels, after ionizing radiation is absorbed, free-radical chain-polymerization of soluble acrylic monomers occurs to form an insoluble polymer. The BANG polymer gel dosimeters used in these measurements allow high resolution, precise, and accurate three-dimensional determination of dosimetry from a given source. Re-188 liquid balloons, with or without an interposed metallic stent, were positioned inside thin walled tubes placed in such a polymer dosimeter to deliver a prescribed dose (e.g., 15 Gy at 0.5 mm). After removing the balloon source, each irradiated sample was mounted in the optical scanner for scanning, utilizing a single compressed He-Ne laser beam and a single photodiode. In the absence of a stent, doses at points along the balloon axis, at radial distance 0.5 mm from the balloon surface and at least 2.5 mm from the balloon ends, are within 90% of the maximum dose. This uniformity of axial dose is independent of the balloon diameter and length. Dose rate and dose uniformity for intravascular brachytherapy with Re-188 balloon are altered by the presence of stent. The dose reduction by the stent is rather constant (13%-15%) at different radial distances. However, dose inhomogeneity caused by the stent decreases rapidly with radial distance.

Deposition of (90)YPO(4) and (144)CePO(4) radioisotopes on polymer surfaces for radiation delivery devices.

Intravascular irradiation with beta emitters inhibits restenosis in arteries after balloon angioplasty or stent implantation. Yttrium-90 ((90)Y, T(1/2)=64 h) and cerium-144 ((144)Ce, T(1/2)=286 d) emit beta particles (E(max)=2.28--3.50 MeV) having an ideal energy range for brachytherapy delivery system. In this article, a previously reported method for depositing (32)P on poly(ethylene terephtalate) (PET) surfaces is generalized and modifications that allow deposition of other beta-emitting radioisotopes, such as (90)Y and (144)Ce, are demonstrated. PET films were first coated with chitosan hydrogel and then adsorbed different amounts of phosphoric acid (PA) in aqueous solutions. Yttrium was deposited onto the surface as YPO(4) after the films were immersed in YCl(3) solutions. 1 muCi (90)YCl(3) (2 x 10(-9) g) was used in each sample as a tracer for measuring the deposition efficiency, which is defined as the percentage of YCl(3) deposited on the surface compared to the amount of YCl(3) in solutions before the deposition. In order to improve the safety of brachytherapy treatments, polyurethanes were used to seal the deposited radioisotopes on the surface to minimize the leakage of the isotopes into the patients. The generality of this method presented here for a wide variety of particular radioisotopic components allows design of a broad range of versatile radioisotope sources.