Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch

ObjectiveClinical 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.MethodsRight 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.ResultsEpicardial 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 (