Optimization of drug‐eluting balloon use for safety and efficacy: Evaluation of the 2nd generation paclitaxel‐eluting DIOR‐balloon in porcine coronary arteries

Abstract Objectives : The aim of this preclinical study was to optimize the use of drug‐eluting balloon (DEB) DIOR 2nd generation by measurements of tissue and plasma paclitaxel concentrations in porcine coronary artery overstretch and prove efficacy in inhibition of neointimal growth without complementary use of stent. Background : The usually recommended DEB 60 sec inflation time causes prolonged ischemia and arterial injury. Methods : Tissue, plasma, and balloon surface concentrations of paclitaxel were measured in pigs 45 min and 12 hr after balloon inflation times of 15, 20, 30, 45, and 60 sec. Extent of neointimal hyperplasia was compared using DIOR 2nd generation or noncoated balloon at two‐week follow‐up. Paclitaxel was replaced by fluorescent paclitaxel derivative in DEB and DES to demonstrate the distribution of the drug in arterial wall. Results : DIOR 2nd generation DEB provided 29 ± 3 μM/L, 52 ± 6 μM/L, 196 ± 44 μM/L, 202 ± 36 μM/L, and 184 ± 59 μM/L paclitaxel to the vessel wall after 15, 20, 30, 45, and 60 sec of dilation, reaching plateau at 30 sec inflation time. Paclitaxel penetrated up to 2 mm tissue deepness. Measurable plasma paclitaxel level (45 ± 28 ng/mL) was found only after 60 sec balloon inflation time. At follow‐up, the dilated arterial segment neointimal area and maximal neointimal thickness were significantly smaller with DIOR vs. uncoated balloon use. Fluorescence images of DIOR showed a homogenous distribution of the drug on the vessel, in contrast with DES. Conclusion : Using the DIOR 2nd generation DEB, a maximal balloon inflation time of 30–45 sec is optimal, reducing effectively the neointimal hyperplasia. © 2010 Wiley‐Liss, Inc.