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

详细信息    查看全文

• 作者：Eunah Kang ; Kumar Vedantham ; Xin Long ; Maria Dadara ; Il-Keun Kwon ; Michael Sturek ; Kinam Park
• 刊名：Molecular Pharmaceutics
• 出版年：2009
• 出版时间：August 3, 2009
• 年：2009
• 卷：6
• 期：4
• 页码：1110-1117
• 全文大小：236K
• 年卷期：v.6,no.4(August 3, 2009)
• ISSN：1543-8392

文摘

1,3-Dipropyl-8-cyclopentyl xanthine (DPCPX) is a highly selective antagonist of the adenosine A₁ receptor (A₁R). The A₁R 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.