Drug release mechanisms of steroid eluting rings in cardiac pacemaker lead electrodes

This paper reports on the drug release mechanisms of silicone structures with embedded steroids applied in pacing leads. Different derivatives of the steroid dexamethasone, which is associated with the reduction of acute stimulation thresholds, were evaluated together with different matrix based release control mechanisms with the target to potentially match optimal drug release rates during the first month after implantation. By incorporating dexamethasone-21-dihydrogen phosphate in silicone matrices in combination with release rate adaption layers, almost continuous release rates were obtained under physiological test settings.

[1]  E J Topol,et al.  Sustained local delivery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model. , 1997, Journal of the American College of Cardiology.

[2]  A. Oto,et al.  Long-term clinical experience with a steroid-eluting active fixation ventricular electrode in children. , 1997, The American journal of cardiology.

[3]  S. K. Chandrasekaran,et al.  Use of osmotically active therapeutic agents in monolithic systems , 1980 .

[4]  H. Mond,et al.  A Comparative Study of the Action of Dexamethasone Sodium Phosphate and Dexamethasone Acetate in Steroid‐Eluting Pacemaker Leads , 2005, Pacing and clinical electrophysiology : PACE.

[5]  H. Mond,et al.  Rapid Decline in Acute Stimulation Thresholds with Steroid‐Eluting Active‐Fixation Pacing Leads , 2005, Pacing and clinical electrophysiology : PACE.

[6]  M. Byrne,et al.  Controlled drug release from contact lenses: A comprehensive review from 1965-present , 2011 .

[7]  HARRY G. MONO,et al.  The Electrode‐Tissue Interface: The Revolutionary Role of Steroid Elution , 1992, Pacing and clinical electrophysiology : PACE.

[8]  H. Bonnemeier,et al.  Long‐Term Superiority of Steroid Elution in Atrial Active Fixation Platinum Leads , 2000, Pacing and clinical electrophysiology : PACE.

[9]  B. Gerritse,et al.  A 12-year experience of bipolar steroid-eluting epicardial pacing leads in children. , 2008, The Annals of thoracic surgery.

[10]  T. Higuchi.  MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[11]  Diane J. Burgess,et al.  Evaluation of in vivo-in vitro release of dexamethasone from PLGA microspheres. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[12]  A. Moritz,et al.  Long-term follow-up after steroid-eluting epicardial pacemaker implantation in young children: a single centre experience. , 2010, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[13]  A. Chauhan,et al.  Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[14]  J. Triedman,et al.  Comparison of Modern Steroid-Eluting Epicardial and Thin Transvenous Pacemaker Leads in Pediatric and Congenital Heart Disease Patients , 2005, Journal of Interventional Cardiac Electrophysiology.

[15]  Delon Wu,et al.  Long‐Term Performance of Transvenous, Steroid‐Eluting, High Impedance, Passive‐Fixation Ventricular Pacing Leads , 2004, Pacing and clinical electrophysiology : PACE.

[16]  G. Kay,et al.  Active Fixation Atrial Leads: Randomized Comparison of Two Lead Designs , 1989, Pacing and clinical electrophysiology : PACE.

[17]  W. Spencer,et al.  Steroid elution improves the stimulation threshold in an active-fixation atrial permanent pacing lead. A randomized, controlled study. Model 4068 Investigators. , 1995, Circulation.