Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model

Nicholas N. Kipshidze, Thomas R. Porter, George Dangas, Hamid Yazdi, Fermin Tio, Feng Xie, David Hellinga, Roswitha Wolfram, Rufus Seabron, Ron Waksman, Alexander Abizaid, Gary Roubin, Sriram Iyer, Antonio Colombo, Martin B. Leon, Jeffrey W. Moses, Patrick Iversen

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 ± 0.84 vs. 4.77 ± 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalCatheterization and Cardiovascular Interventions
Volume64
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Rapamycin
  • Restenosis
  • Site-specific drug delivery
  • Stents

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model'. Together they form a unique fingerprint.

Cite this