Drug-eluting stent for delivery of signal pathway-specific 1,3-dipropyl-8-cyclopentyl xanthine

Eunah Kang, Kumar Vedantham, Xin Long, Maria Dadara, Il Keun Kwon, Michael Sturek, Kinam Park

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

1,3-Dipropyl-8-cyclopentyl xanthine (DPCPX) is a highly selective antagonist of the adenosine A1 receptor (A1R). The A 1R mediates mitogenic effects of adenosine in coronary artery smooth muscle cells (CASMC). DPCPX plays a role as an antimitogen and reduces CASMC proliferation by the blockage of A1R. A drug-eluting stent (DES) loaded with DPCPX was prepared. The water solubility of DPCPX is 1.6 μg/mL at pH 3-9, and 38.1 ± 2.3 μg/mL at pH 11. A series of DPCPX-eluting stents were formulated in polyurethane (PU) films with different dose densities and film thicknesses. The release of DPCPX from the PU-coated stents was nearly linear. The release rate and duration were effectively controlled by adjusting the film thickness with the same drug concentration. The eluted DPCPX from the PU films was effective in preventing CASMC proliferation, regardless of stimulation by 2-chloro-N-6-cyclopentyladenosine (CCPA), a highly selective A1R agonist. A1R specific antagonist DPCPX was effective in preventing CASMC proliferation and holds great promise for intracoronary delivery from DESs to test the role of the A1R signaling pathway for prevention of in-stent restenosis.

Original languageEnglish (US)
Pages (from-to)1110-1117
Number of pages8
JournalMolecular Pharmaceutics
Volume6
Issue number4
DOIs
StatePublished - Aug 3 2009

Keywords

  • 1,3-Dipropyl-8-cyclopentyl xanthine
  • Adenosine receptor
  • Coronary artery smooth muscle cells
  • Drug eluting stent
  • Restenosis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

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