Effects of different application parameters on penetration characteristics and arterial vessel wall integrity after local nanoparticle delivery using a porous balloon catheter

Catheter-based local delivery of drug loaded nanoparticles agents offers a potential therapeutic approach to reducing restenosis. However, high delivery pressures and large volumes of infusates may cause severe vascular damage and increase intimal thickening. Therefore, we investigated the penetration pattern and vessel wall integrity of fluorescence-labelled nanoparticles (217 nm in diameter) into the non-atherosclerotic aorta abdominalis of New Zealand white rabbits in dependence of the volume (2.5 and 5 ml) and concentration (0.5 and 1 mg/ml) of the nanoparticle suspension, as well as the infusion pressure (2 and 4 atm) using a channelled balloon catheter (SCIMED REMEDY(TM) model RC 20/2.5). The location and penetration characteristics of nanoparticles in the arterial vessel wall were visualized using confocal laser scanning microscopy and transmission electron microscopy (TEM). Catheter design and infusion pressure form a radial particle stream through intima and media into the adventitial layer of the aorta abdominalis. Infusion pressures of 4 atm in combination with high particle concentrations lead to effective nanoparticle delivery without severe vessel wall disruptions. Endothelium of the treated vessel segments was slightly affected during catheter insertion showing partly denudation of the innermost cell layer. TEM micrographs underlines transport functional properties of the vasa vasorum inside the vessel wall. Consequently, local delivery efficiency of nanoparticulate carriers is critically affected by infusion pressure, and concentration of carrier suspensions. These factors need to be taken into consideration for the design of in vivo experiments. (C) 2004 Elsevier B.V. All rights reserved.