984-30 Use of Electroporated Platelets as a Novel Drug Delivery System in Preventing Complications of Coronary Angioplasty

Abstract

Acute occlusion and more importantly late restenosis remain important limitations of various percutaneous intervention techniques. Local delivery of agents is a theoretically appealing method of preventing these complications. Due to their affinity for areas of arterial injury, platelets may serve as an ideal delivery vehicle. Compounds can be entrapped within platelets during exposure of the cells to a sequence of high voltage discharges. This process, termed electroporation, occurs via simple diffusion through field induced membrane pores. We studied the prostacyclin analogue, lloprost, to test the potential of this system. We evaluated the extent of platelet deposition at the site of balloon-mediated vascular injury in normal rabbit femoral arteries. Arterial injury was performed to the femoral arteries bilaterally using a 2.5 mm balloon in 12 NZW rabbits. Either normal (control), electroporated without lloprost (sham), or electroporated with lloprost (iloprost) donor platelets (5 × 10 8 ) were infused at the time of the balloon injury. Platelets were electroporated with 5 cycles of high voltage discharges in a high potassium medium, and resealed by incubation at 37°C for 40 min. For lloprost loading, lloprost at a concentration 20 μg/ml was added to the medium. Quantification of platelet deposition at the site of arterial injury was obtained using indium- 111 labeled platelets infused 1/2 hour prior to balloon injury. Involved arterial segments were excised 2 hours after arterial injury. The results are expressed as platelets per centimeter of artery (graph). Further, preliminary results in an atherosclerotic rabbit model demonstrated a 64% reduction in platelet deposition using lloprost loaded platelets. Taking advantage of a natural physiologic process after arterial injury, this delivery system offers a unique “piggy-back” mechanism of drug delivery. Platelet encapsulation with lloprost and other agents deserves further study.