title: Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch.
abstract: OBJECTIVE
  Clinical studies have demonstrated the efficacy of oral and intravenous amiodarone therapy to prevent postoperative atrial fibrillation. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. This study addressed the hypothesis that atrium-specific drug delivery through an amiodarone-eluting epicardial patch reduces vulnerability to atrial tachyarrhythmias, whereas ventricular and plasma drug concentrations are minimized.
  
  
  METHODS
  Right atrial epicardiums of goats were fitted with electrodes and a bilayered patch (poly[ethylene glycol]-based matrix and poly[lactide-co-caprolactone] backing layer) loaded with amiodarone (10 mg per patch, n = 10) or without drug (n = 6). Electrophysiologic parameters (atrial effective refractory period, conduction time, and rapid atrial response to burst pacing) and amiodarone levels in plasma and tissue were measured during 1 month's follow-up.
  
  
  RESULTS
  Epicardial application of amiodarone-eluting patches produced persistently higher drug concentrations in the right atrium than in the left atrium, ventricles, and extracardiac tissues by 2 to 4 orders of magnitude. Atrial effective refractory period and conduction time increased, whereas rapid atrial response inducibility decreased significantly (P < .05) during the 1-month follow-up compared with that seen in animals treated with drug-free patches. Amiodarone concentrations in plasma remained undetectably low (<10 ng/mL).
  
  
  CONCLUSIONS
  Atrium-specific drug delivery through an amiodarone-eluting patch produces therapeutic atrial drug concentrations, whereas ventricular and systemic drug levels are minimized. This study demonstrates that sustained targeted drug delivery to a specific heart chamber is feasible and might reduce the risk for ventricular and extracardiac adverse effects. Epicardial application of amiodarone-eluting patches is a promising strategy to prevent postoperative atrial fibrillation.
authors.affiliation: Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands. r.bolderman@ctc.unimaas.nl
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bolderman
authors.forename: Peter
authors.initials: P
authors.lastname: Bruin
authors.forename: J J Rob
authors.initials: JJ
authors.lastname: Hermans
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Boerakker
authors.forename: Aylvin A
authors.initials: AA
authors.lastname: Dias
authors.forename: Frederik H
authors.initials: FH
authors.lastname: van der Veen
authors.forename: Jos G
authors.initials: JG
authors.lastname: Maessen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000287:Administration, Topical; D000638:Amiodarone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D006041:Goats; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007700:Kinetics; D010496:Pericardium; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000889:Anti-Arrhythmia Agents; D004304:Dosage Forms; D004337:Drug Carriers; D011092:Polyethylene Glycols; D000638:Amiodarone