Targeted vascular delivery of antisense molecules using intravenous microbubbles

Thomas Richard Porter, Feng Xie, Derek Knapp, Patrick Iversen, Luis A Marky, Jeane M. Tsutsui, Souvik Maiti, John Lof, Stanley J Radio, Nicholas Kipshidze

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Objective: Perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles bind the antisense to the c-myc protooncogene (anti-c-myc) which prevents neointimal hyperplasia following vascular endothelial injury. The microbubbles also adhere to sites of damaged vascular endothelium and thus may be a method of systemically targeting delivery of anti-c-myc. Methods: Laser scanning microscopy was performed on the aorta of 10 mice (five which were complement depleted) that received intravenous FITC-PESDA following aortic endothelial injury. C-myc expression was quantified following selective intracoronary injury in nine pigs that received intravenous (IV) anti-c-myc bound to PESDA. Finally, neointimal formation was measured following intracoronary stent deployment in 30 pigs that received either IV anti-c-myc alone or the same dose bound to PESDA. Results: Fluorescent microscopy confirmed selective PESDA microbubble adherence to aortic endothelium in all mice with aortic injury. This binding was nearly abolished when serum complement was depleted prior to injury. C-myc expression at the site of coronary endothelial injury was significantly lower in pigs treated with systemic anti-c-myc bound to PESDA. There was a 33% reduction in % stenosis and a 28% reduction in intimal area at 45 days post-stent deployment in pigs that received IV antisense plus PESDA. The stent margins also had reduced neointimal formation. Conclusion: Systemic administration of anti-c-myc bound to PESDA microbubbles may be a good method for preventing coronary neointimal formation within and around implanted stents.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalCardiovascular Revascularization Medicine
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2006

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Keywords

  • Drug delivery
  • Intimal hyperplasia
  • Microbubbles

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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