MICROPARTICLE DEPOSITION IN PERIARTERIAL MICROVASCULATURE AND INTRAMURAL DISSECTIONS AFTER POROUS BALLOON DELIVERY INTO ATHEROSCLEROTIC VESSELS - QUANTITATION AND LOCALIZATION BY CONFOCAL SCANNING LASER MICROSCOPY

Local delivery of pharmacologic or genetic agents with a porous balloo n catheter offers a potential therapeutic approach to reducing resteno sis and atherosclerosis and minimizing undesirable systemic toxicity. However, the delivery efficiency and intramural retention of liquid ag ents is low. The local intramural delivery and prolonged retention of 5 mu m microparticles (MP) has been described previously. The current study was designed to evaluate the distribution of locally delivered M Ps and to determine the effects of MP size and infusion pressure on in tramural delivery efficiency. A 1% suspension of fluorescent, latex MP s (1 or 4.5 mu m in diameter) was infused at either 3 or 6 atm into at herosclerotic rabbit femoral arteries (n = 32) immediately after angio plasty. Four groups of arteries were evaluated: 1) 1 mu m MPs infused at 3 atm; 2) 1 mu m MPs at 6 atm; 3) 4.5 mu m MPs at 3 atm; and 4) 4.5 mu m MPs at 6 atm. The location of MPs was evaluated by fluorescent a nd light microscopy and confocal laser scanning microscopy. The tissue was dissolved and the delivered MPs quantified. All groups manifested numerous MPs within the vasa vasorum and periadventitial microvascula ture, with a substantially lesser number within the neointimal and med ial layers. The intramural deposition of the MPs was associated with d issection within the intima or media caused by the antecedent angiopla sty or local delivery, indicating that an intact vessel wall is an ana tomic barrier to MP delivery. The median values of fractional intramur al delivery, defined as the percentage of infused MPs retained within the arterial wall, were 0.059%, 0.071%, 0.047%, and 0.062% for groups 1 through 4, respectively (p not significant [NS]). The values of intr amural particle concentration, expressed as the total number of MPs pe r weight of arterial tissue, were 55, 65, 1.5, and 1.2 x 10(4) MPs/mg for groups 1 through 4, respectively (p < 0.001 for 1 mu m vs 4.5 mu m MPs). Although more 1 mu m MPs were delivered than 4.5 mu m MPs, the fractional intramural delivery was unaffected by particle size or infu sion pressure. The local delivery of MPs at atherosclerotic sites afte r angioplasty is characterized by fractional intramural delivery value s similar to values of nonparticulate agents, with few MPs deposited i nto intima or media in the absence of a dissection caused by the antec edent angioplasty or the delivery procedure itself.