Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug‐coated balloon in a swine femoral artery model

This study was designed to evaluate the safety of a novel drug-coated balloon (DCB) with 2 µg/mm(2) paclitaxel and a carrier comprised of polysorbate and sorbitol in a swine femoral artery model.DCB have emerged as a therapeutic alternative in the treatment of peripheral vascular disease.The femoral arteries of 45 swine were treated with low pressure balloon inflation either 1× clinical dose (single inflation, 2 µg/mm(2) paclitaxel) or 4× dose (2 DCBs, each with 4 µg/mm(2) paclitaxel) or control (uncoated) balloons. The treated arteries, downstream vascular beds, and organs were assessed histologically at 28, 90, and 180-days. Twenty-four swine were treated with 1× dose for pharmacokinetic analysis through 30 days.Arterial tissue paclitaxel concentration was 58.8 ± 54.2 ng/mg at 1-hr and 0.3 ± 0.4 ng/mg at 30 days, whereas plasma paclitaxel could no longer be detected after 1 day. The treated arteries displayed minimal endothelial loss, fibrin deposition, and inflammation with long-term dose-dependent drug effect (medial smooth muscle cell loss) peaking at 90 days for both 1× (1.1 ± 1.4 vs. 0.0 ± 0.0, P = 0.008) and 4× dose (2.0 ± 1.5 vs. 0.0 ± 0.0, P < 0.001). In parallel, healing of the treated arteries was evident by significantly greater medial proteoglycan and collagen deposition at 180 days. No evidence of ischemia from downstream emboli or systemic toxicity was observed even for 4× DCB groups.The findings indicate desired pharmacologic levels with biologic effects at early and healing at late time points in the treated arteries, without evidence of significant downstream emboli or systemic toxicity, consistent with safety of the Lutonix DCB.