Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch.
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.
Bolderman
Robert W
RW
Department of Cardiothoracic Surgery, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands. r.bolderman@ctc.unimaas.nl
Bruin
Peter
P
Hermans
J J Rob
JJ
Boerakker
Mark J
MJ
Dias
Aylvin A
AA
van der Veen
Frederik H
FH
Maessen
Jos G
JG
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
D000889:Anti-Arrhythmia Agents; D004304:Dosage Forms; D004337:Drug Carriers; D011092:Polyethylene Glycols; D000638:Amiodarone