Local drug delivery: Impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall

A. Baumbach, C. Herdeg, M. Kluge, M. Oberhoff, M. Lerch, K. K. Haase, C. Wolter, S. Schroder, K. R. Karsch, A. W. Heldman, J. A. Brinker

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Injection parameters for local drug delivery are frequently determined by studies with marker substances. However, the pharmacologic properties of the actual drug may influence delivery efficiency and lead to different results. Aim of this study was to assess the delivery capacities of two device-drug combinations in order to verify this approach for further in vivo studies. Tritiated (3H) preparations (5 ml) of the hydrophylic low- molecular-weight heparin reviparin and the lipophilic taxane paclitaxel were injected into the left anterior descending artery of freshly explanted porcine hearts with the Infusasleeve II catheter system. A balloon support pressure of 6 atm and infusion pressures of 40, 60, 80, or 100 psi were used. In three additional groups, reviparin was injected following stent implantation and paclitaxel was injected prior to or following stent implantation. Arteries along with surrounding myocardium were harvested. The artery was carefully dissected, and artery and myocardium were separately homogenized, and activity was measured. Of the totally delivered activity, 0.09% ± 0.03% (40 psi) to 0.17% ± 0.13% (100 psi) of reviparin and 2.03% ± 0.67% (60 psi) to 2.68% ± 1.57% (100 psi) of paclitaxel were found in the vessel wall. The results for different injection pressures were not significantly different for either drug. The percentage activity delivered to the vessel wall was substantially larger in the paclitaxel group as compared to reviparin delivery (P < 0.01 at 60, 80, and 100 psi). The mean concentration of reviparin in the artery was 20 to 33 times higher than in the myocardium. For paclitaxel the factors were 110 to 243. Stent implantation prior to or following local delivery did not result in a different delivery efficiency. The results demonstrate that the characteristics of the delivered drug contribute largely to the delivery efficiency. Using identical injection parameters, drug concentrations in the arterial wall were significantly higher for the lipophilic paclitaxel as compared to the hydrophilic reviparin. Stenting of the artery did not influence delivery efficiency.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalCatheterization and Cardiovascular Interventions
Volume47
Issue number1
DOIs
StatePublished - Jul 14 1999
Externally publishedYes

Keywords

  • Local drug delivery
  • Paclitaxel
  • PTCA
  • Radiolabelled
  • Reviparin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Local drug delivery: Impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall'. Together they form a unique fingerprint.

  • Cite this

    Baumbach, A., Herdeg, C., Kluge, M., Oberhoff, M., Lerch, M., Haase, K. K., Wolter, C., Schroder, S., Karsch, K. R., Heldman, A. W., & Brinker, J. A. (1999). Local drug delivery: Impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall. Catheterization and Cardiovascular Interventions, 47(1), 102-108. https://doi.org/10.1002/(SICI)1522-726X(199905)47:1<102::AID-CCD22>3.0.CO;2-G