Regional and arterial localization of radioactive microparticles after local delivery by unsupported or supported porous balloon catheters

Robert L. Wilensky, Keith L. March, Irmina Gradus-Pizlo, Donald Schauwecker, Mary Beth Michaels, Janine Robinson, Kathy Carlson, David R. Hathaway

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Catheter-mediated intramural delivery of pharmaceutical agents after angioplasty is a potential method to reduce postangioplasty restenosis. The efficacy of such delivery has been limited both by an incomplete initial intramural deposition of delivered agents and by rapid diffusion of soluble agents from the site of delivery. The local delivery of microparticulate agents results in prolonged retention of material at the delivery site. Accordingly this study was designed to evaluate the complementary issue of the initial delivery efficiency and pattern of localization of microparticles after local catheter-mediated delivery with two types of porous balloons. These two types were a "standard" porous balloon (PB) in which hydraulic pressure both inflated the balloon and infused the agents and a porous balloon with a mechanical undergirding that permitted mechanical expansion (PB/ME) before agent infusion. Radioactive cerium 141-labeled microparticles (11.4 μm diameter) were locally delivered into atherosclerotic rabbit femoral arteries after angioplasty to test the hypothesis that use of the PB/ME apparatus would yield enhanced intramural particle deposition and decreased systemic administration by increased balloon-wall contact before microparticle infusion. Six animals underwent infusion with the PB catheter, and seven animals underwent infusion with the PB/ME catheter. An image of the in vivo particle distribution was obtained with a gamma camera during infusion, immediately after infusion, and 1, 3, and 7 days after infusion. Tissue samples from the artery, periadventitia, thigh, calf, and foot musculature, and liver were obtained at animal death, and retained radioactivity was measured with a well counter. Microparticle delivery was evaluated according to two parameters: (1) the fractional regional delivery, which is the fraction of microparticles delivered into the region surrounding the balloon in the upper leg as measured by the γ camera, and (2) the fractional intramural delivery, which is the fraction of microparticles specifically delivered into the vascular tissue as measured by direct tissue counting. The fractional regional delivery was 99.9% ± 0.1% with the PB/ME and 84.2% ± 4.2% with the standard PB (p = 0.008). Distal delivery of microparticles was accordingly lower after infusion with the PB/ME catheter; radioactivity at 7 days in the foot averaged 9 ± 4.5 counts/min/mg tissue versus 186 ± 67 counts/min/mg after infusion with the PB catheter (p = 0.01). Despite this difference in systemic delivery the fractional intramural delivery was similar for both infusion devices. Only 0.16% ± 0.04% was deposited into the arterial wall by the PB/ME, and 0.14% ± 0.05% was deposited by the PB (p = NS). The remaining microparticles were found in the periadventitia and overlying musculature. Retention of microparticles at 7 days after the delivery exceeded 90% with each catheter. In conclusion, local delivery and retention of 11.4 μm microparticles at high concentration into and around the arterial wall is feasible but is characterized by a low intramural delivery efficiency (<0.17%). Most of the microparticles are rapidly delivered into the periadventitia and overlying musculature. Therefore the selection of pharmaceutical agents or genetic material delivered locally to reduce restenosis with such catheters must take into account any effects of the chosen agents on overlying tissue.

Original languageEnglish (US)
Pages (from-to)852-859
Number of pages8
JournalAmerican Heart Journal
Volume129
Issue number5
DOIs
StatePublished - May 1995

    Fingerprint

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Wilensky, R. L., March, K. L., Gradus-Pizlo, I., Schauwecker, D., Michaels, M. B., Robinson, J., Carlson, K., & Hathaway, D. R. (1995). Regional and arterial localization of radioactive microparticles after local delivery by unsupported or supported porous balloon catheters. American Heart Journal, 129(5), 852-859. https://doi.org/10.1016/0002-8703(95)90103-5