HYDROGEL-BASED ANTI-ARRYTHMIC CARDIAC DRUG DELIVERY

Arthur Coury ,  Michael Philbrook ,  Robert Miller ,  Kevin Skinner ,  Jude Colt ,  Rubina Corazzini ,  Li-Ping Yu ,  Kenneth Messier ,  Peter Jarrett ,  James Burns 

Genzyme Corp., 500 Kendall Street, Cambridge, MA 02142, United States

Abstract

Atrial fibrillation (AF) is a common and severe complication of thoracic surgeries including coronary artery bypass, heart valve replacement and lung resection. Prophylactic treatment of surgery patients with anti-arrythmic drugs is not widely used because of complications from systemic delivery and coordination requirements between the patient's cardiologist and surgeon. A safe, effective anti-arrythmic, prophylactic drug applied at surgery would potentially find broad application among cardiac surgeons. The approach described here uses a photopolymerized, tissue-adherent, resorbable hydrogel containing the anti-arrythmic drug, amiodarone applied to the epicardium for sustained release. The hydrogel is a member of a family of compositions based on a macromer comprising a poly(oxyethylene) core, flanking oligomers of hydrolytically degradable groups and end-caps of acrylate ester. These hydrogels have successfully released and expressed a variety of substances including small molecules, proteins and genes. The current application technique involves deposition of a primer on the tissue, brushing in and dripping on the drug-containing topcoat and illuminating with visible light to produce an adherent composite for programmed drug release into the tissue. To date, in vitro studies have established that drug release should achieve the targeted two-week minimum delivery. In vivo, one-week canine studies have shown that tissue levels of amiodarone expected to be therapeutic were achieved. Longer-term canine studies indicated sustained elevation of atrial effective refractory period (AERP) in the treated cohort. AERP elevation is a surrogate marker for potential suppression of post-surgical AF. Future studies will focus on gel clearance and tissue healing.

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Presentation: invited oral at E-MRS Fall Meeting 2004, Symposium B, by Arthur Coury
See On-line Journal of E-MRS Fall Meeting 2004

Submitted: 2004-05-17 00:22
Revised:   2009-06-08 12:55
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