Abstract
Local drug delivery is an attractive approach to the associated problems of percutaneous transluminal coronary angioplasty (PTCA), including arterial injury. The objective of the present research was to deliver a high concentration of a potent anti-thrombin agent, argatroban (ARG), to the vessel wall in order to reduce arterial injury. Local delivery was accomplished by the ionic attachment of drug particles to a modified balloon surface. Surface graft polymerization of ionic monomers to a high-density poly(ethylene) (PE) substrate was performed utilizing ultra-violet (UV) methods. Acrylic acid (AAc) and 2(dimethylamino) ethyl methacrylate (DMAEMA) were successfully grafted onto PE surfaces. Surface grafting was verified by contact angle, X-ray photoelectron spectroscopy, and zeta potential measurements. The amount of ARG adsorbed onto the modified PE surface was highly dependent on the pH of the drug media for both anionic and cationic grafted monomers. The efficacy of local drug delivery to the arterial wall was analyzed using drug-immobilized PE balloon catheters in the rabbit common carotid artery model. High concentrations of ARG (280 nmol/g tissue) were found within the ballooned arterial segment immediately after angioplasty, followed by a decrease after blood flow was restored.
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