Microparticle deposition in periarterial microvasculature and intramural dissections after porous balloon delivery into atherosclerotic vessels: Quantitation and localization by confocal scanning laser microscopy

Abstract

Local delivery of pharmacologic or genetic agents with a porous balloon catheter offers a potential therapeutic approach to reducing restenosis and atherosclerosis and minimizing undesirable systemic toxicity. However, the delivery efficiency and intramural retention of liquid agents is low. The local intramural delivery and prolonged retention of 5 μm microparticles (MP) has been described previously. The current study was designed to evaluate the distribution of locally delivered MPs and to determine the effects of MP size and infusion pressure on intramural delivery efficiency. A 1% suspension of fluorescent, latex MPs (1 or 4.5 μm in diameter) was infused at either 3 or 6 atm into atherosclerotic rabbit femoral arteries ( n = 32) immediately after angioplasty. Four groups of arteries were evaluated: 1) 1 μm MPs infused at 3 atm; 2) 1 μm MPs at 6 atm; 3) 4.5 μm MPs at 3 atm; and 4) 4.5 μm MPs at 6 atm. The location of MPs was evaluated by fluorescent and 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 microvasculature, with a substantially lesser number within the neointimal and medial layers. The intramural deposition of the MPs was associated with dissection within the intima or media caused by the antecedent angioplasty or local delivery, indicating that an intact vessel wall is an anatomic barrier to MP delivery. The median values of fractional intramural 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 intramural particle concentration, expressed as the total number of MPs per weight of arterial tissue, were 55, 65, 1.5, and 1.2 × 10 4 MPs/mg for groups 1 through 4, respectively ( p < 0.001 for 1 μm vs 4.5 μm MPs). Although more 1 μm MPs were delivered than 4.5 μm MPs, the fractional intramural delivery was unaffected by particle size or infusion pressure. The local delivery of MPs at atherosclerotic sites after angioplasty is characterized by fractional intramural delivery values similar to values of nonparticulate agents, with few MPs deposited into intima or media in the absence of a dissection caused by the antecedent angioplasty or the delivery procedure itself.