Abstract
Restenosis remains the major limitation of percutaneous transluminal angioplasty (PTA) and stenting in the treatment of patients with atherosclerotic disease. Catheter-based local delivery of pharmacologic agents offers a potential therapeutic approach to reducing restenosis and minimizing undesirable systemic side effects. However, the intramural retention of liquid agents is low. Therefore, to achieve a sustained and regional release of the therapeutic agent it must be encapsulated in nanoparticle carrier systems. The purpose of this study was to investigate the size dependence of the penetration of nanoparticles after local delivery into the vessel wall of the aorta abdominalis of New Zealand white rabbits. Two milliliters of a 0.025% fluorescence-labeled polystyrene nanoparticle suspension with diameters ranging from 110 to 514 nm were infused at 2 atm and at constant PTA pressure of 8 atm into the aorta abdominalis. After the infused segments were removed, the location of nanoparticles was visualized using confocal laser scanning microscopy and transmission electron microscopy. The study demonstrates a size-dependent nanoparticle penetration into the intact vessel wall. While nanoparticles of about 100 and 200 nm were deposited in the inner regions of the vessel wall, 514-nm nanoparticles accumulated primarily at the luminal surface of the aorta. The observations confirm that size plays a critical role in the distribution of particles in the arterial vessel wall. It is additionally influenced by the formation of pressure-induced infusion channels, as well as by the existence of anatomic barriers, such as plaques, at the luminal surface of the aorta or the connective elastic tissue.