Showing papers by "Ulrich Speck published in 2011"
TL;DR: 2 paclitaxel matrix formulations on angioplasty balloon catheters in vitro were assessed with respect to pharmacokinetics, efficacy and tolerance to determine the minimum effective dose and local toxicity at extremely high dose which is only achieved in experimental studies.
Abstract: Objective:There is little published information regarding the efficacy of paclitaxel-coated balloon catheters except for the iopromide-containing formulation, and less is known about the kind of toxicity at overdose. The aim of our study was to assess 2 different paclitaxel matrix formulations on an
101 citations
TL;DR: After short-term application, paclitaxel and sirolimus show differential, cell-specific effects on EPC and hCASMC and Iopromide used as a coating agent intensifies these effects.
Abstract: Aims EPC and hCASMC play an important role in the pathogenesis of restenosis and stent thrombosis. Drug-coated balloon catheters exert a local, short-term application of antiproliferative agents. This study investigates the time-dependent influence on growth and motility of paclitaxel and sirolimus alone and combined with the coating additive iopromide on EPC and hCASMC. Methods and results Treatment of cultured human EPC and hCASMC with paclitaxel and sirolimus 1.5 and 15 µM for three seconds, three minutes and 24 hours, alone or combined with iopromide 0.197 M, resulted in a concentration- and time- dependent inhibition of proliferation and of migration. Paclitaxel and sirolimus increase apoptosis in either cell type. However, the effects of paclitaxel and sirolimus differed between the cell types: short-term exposure with paclitaxel leads to stronger inhibition of cell-density and apoptosis of hCASMC compared to EPC. In comparison to paclitaxel, short-term incubation with sirolimus showed a more effective inhibition of cell-density and migration as well as increased apoptosis in EPC in contrast to hCASMC. The effects of paclitaxel and sirolimus were increased in combination with iopromide. Interestingly, the antiproliferative effect of the paclitaxel-iopromide formulation on hCASMC was more potent compared to its effect on EPC. Endothelialisation in a porcine coronary stent model was similar with drug-coated balloons and uncoated controls, whereas it was delayed with drug-eluting stents. Conclusion After short-term application, paclitaxel and sirolimus show differential, cell-specific effects on EPC and hCASMC. Iopromide used as a coating agent intensifies these effects.
34 citations
TL;DR: Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug, which may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long- lasting excessive neointimal proliferation, which occurs early after vessel injury.
Abstract: Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.
11 citations
TL;DR: The rationale for the use of paclitaxel-coated balloons, along with a focus on the SeQuent Please balloon catheter system, is reviewed, indicating that restenosis inhibition by immediate drug release is feasible.
Abstract: Endovascular therapy for treatment of arterial obstructions has emerged as one of the most promising techniques in minimally invasive medicine during the last few decades. However, long-term outcome remains an area of concern in many applications. Drug-coated balloons represent an enhancement of the therapeutic repertoire for the interventional cardiologists. Among drug-coated balloons currently available on the market is the the SeQuent™ Please device, a coronary balloon catheter that combines balloon angioplasty with local delivery of paclitaxel. In several small, but randomized, clinical trials, the paclitaxel-coated SeQuent Please balloon catheter system has been shown to be safe and effective in reducing restenosis in patients with coronary in-stent restenosis, indicating that restenosis inhibition by immediate drug release is feasible. This article reviews the rationale for the use of paclitaxel-coated balloons, along with a focus on the SeQuent Please with its concept and the currently available cl...
2 citations
TL;DR: Coating paclitaxel onto the surface of conventional percutaneous transluminal coronary angioplasty balloon catheters with a new coating technique that provides immediate drug release upon inflation was a new approach to preventing restenosis without having to implant a stent.
Abstract: The starting point of percutaneous transluminal coronary angioplasty was defined by Andreas Gruntzig in 1977 [1]. He developed the novel technique of revascularization and established a new speciality – interventional cardiology. Since that time, interventionalists have been confronted with the problems of vessel recoil during the procedure and restenosis within the first 6 months of balloon angioplasty. In spite of progress in some indications, in others these challenges have lost nothing of their significance, motivating investigators to pursue their research efforts with a view to finding new strategies for overcoming these difficulties. Stents proved to be a significant advance in reducing the frequency of restenosis by eliminating elastic recoil and negative remodeling at the treatment site [2]. However, neointimal proliferation is not prevented by stenting, and thus in-stent restenosis became a ‘new’ disease, especially in some patient populations such as diabetics or in certain lesions such as bifurcation, long lesions, lesions in small vessels, total occlusions and diffuse disease [3]. The systemic administration of anti-inflammatory, antiproliferative, anticlotting or other agents before or after balloon dilatation was shown to effectively reduce neointimal hyperplasia in animal models. Clinical use in humans, however, failed to result in adequate restenosis prevention [4]. The advent of drug-eluting stents (DESs) marked a decisive advance, enabling direct transfer of drugs to the target site and prolonged exposure of the vessel wall. Sirolimus and paclitaxel were shown to be effective pharmacological inhibitors of neointimal hyperplasia in vitro and in vivo [5,6]. Stents coated with these agents were successfully used in both the coronary arteries [7] and below the knee [8]. By contrast, use of these stents were not found to be superior to bare-metal stents in femoral and popliteal arteries or in patients with severe diffuse disease and long, complicated lesions [9]. The occurrence of late stent thrombosis, caused by incomplete endothelization of the stent struts and an inflammatory response to the polymer matrix, considerably limited the use of DES [10,11]. Coating paclitaxel onto the surface of conventional percutaneous transluminal coronary angioplasty balloon catheters with a new coating technique that provides immediate drug release upon inflation was a new approach to preventing restenosis without having to implant a stent. The drug is transferred to the dilated segment when the balloon is inflated. An effective local drug concentration is achieved with very low systemic exposure. Paclitaxel admixed to a small amount of the hydrophilic x-ray contrast medium iopromide (Ultravist) emerged as a very effective coating matrix from numerous in vitro and in vivo experiments investigating different coating techniques, the adhesion of paclitaxel to the balloon surface while the catheter is advanced to the lesion, and the release of the active agent into the vessel wall during balloon expansion [12,13]. Balloon catheters coated in this way have a paclitaxel dose of 3 μg/mm of balloon surface and are marketed as Paccocath (Bayer Schering Pharma AG, Germany). 1Department of Radiology, Charite – Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany 2Clinic for Internal Medicine III, Cardiology, Angiology and Intensive Care, University Hospital of Saarland, Homburg/Saar, Germany †Author for correspondence: Tel.: +49 304 5053 9076 Fax: +49 304 5052 7993 E-mail: beatrix.schnorr@charite.de