Pharmacokinetics and tissue localization of antisense oligonucleotides in balloon-injured pig coronary arteries after local delivery with an iontophoretic balloon catheter.

Autor: Robinson KA; Andreas Gruentzig Cardiovascular Center, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. keith_robinson@email.eusch.org, Chronos NA, Schieffer E, Palmer SJ, Cipolla GD, Milner PG, Walsh RG, King SB 3rd
Jazyk: angličtina
Zdroj: Catheterization and cardiovascular diagnosis [Cathet Cardiovasc Diagn] 1997 Jul; Vol. 41 (3), pp. 354-9.
DOI: 10.1002/(sici)1097-0304(199707)41:3<354::aid-ccd18>3.0.co;2-n
Abstrakt: When delivered locally to the arterial wall by passive fluid transfer systems such as perforated balloons, water-soluble compounds in aqueous solution are not readily taken up by tissue, show low levels of cellular localization, and are quickly lost by wash-out. One approach to improve 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 determined the quantity and localization of ODN in the tissue. By radiolabeling, 7.3 +/- 2.4 micrograms 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 delivery to arterial tissue.
Databáze: MEDLINE