Drug-Eluting Stent for Delivery of Signal Pathway-Specific 1,3-Dipropyl-8-cyclopentyl Xanthine

Abstract

1,3-Dipropyl-8-cyclopentyl xanthine (DPCPX) is a highly selective antagonist of the adenosine A(1) receptor (A(1)R). The A(1)R 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 A(1)R. A drug-eluting stent (DES) loaded with DPCPX was prepared. The water solubility of DPCPX is 1.6 microg/mL at pH 3-9, and 38.1 +/- 2.3 microg/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 A(1)R agonist. A(1)R specific antagonist DPCPX was effective in preventing CASMC proliferation and holds great promise for intracoronary delivery from DESs to test the role of the A(1)R signaling pathway for prevention of in-stent restenosis.