PHARMACOKINETICS AND TISSUE LOCALIZATION OF ANTISENSE OLIGONUCLEOTIDES IN BALLOON-INJURED PIG CORONARY-ARTERIES AFTER LOCAL-DELIVERY WITH AN IONTOPHORETIC BALLOON CATHETER

When delivered locally to the arterial wall by passive fluid transfer systems such as perforated balloons, water-soluble compounds in aqueou s solution are not readily taken up by tissue, show low levels of cell ular localization, and are quickly lost by wash-out. One approach to i mprove delivery is addition of an ''active'' component to the catheter system to change the nature of the drug-to-tissue interaction, Using an iontophoretic balloon catheter to deliver antisense oligonucleotide (ODN) to pig coronary arteries after balloon angioplasty, we determin ed the quantity and localization of ODN in the tissue. By radiolabelin g, 7.3 +/- 2.4 mu g ODN was present at 30 min,1.5 +/- 0.6 at 2 h, 0.52 +/- 0.35 at 24 h, and 0.26 +/- 0.11 at 7 d. By fluorescent labeling, circumferential medial uptake and adventitial delivery at the site of medial injury was observed, with primarily cellular localization, The iontophoretic catheter thus appears to be a useful device for ODN deli very to arterial tissue. (C) 1997 Wiley-Liss, Inc.