Local Delivery of Nadroparin via Hydrogel-coated Angioplasty Balloon: Effect on Platelet Deposition and Smooth Muscle Cell Proliferation—An Experimental Study

Abstract

To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.