Drug Loss at Arterial Bends Can Dominate Off-Target Drug Delivery by Paclitaxel-Coated Balloons.

Abstract

Background/Objective: Paclitaxel-coated balloons (PCBs) can deliver efficacious drug concentrations to treated arterial segments but are known to exhibit high tracking losses. We aimed to define the governing factors impacting tracking loss and to contrast its drug distribution consequences with those of PCB inflation at the treatment site. Methods: Four naïve and four in-stent restenosis (ISR) porcine superficial femoral arteries (SFA) were treated with PCBs, and plasma samples were collected post-tracking and post-inflation. Animals were sacrificed <1 h post-intervention, and local, upstream, and downstream tissues were collected for paclitaxel quantification. Computationally driven quantitative benchtop-tracking and frictional PCB-sliding experiments modeled paclitaxel loss and delivery to upstream tissue. Results: Paclitaxel concentrations in plasma peaked pre-inflation and declined 30-fold immediately post-inflation. Correspondingly, losses of 30% and 1% of nominal PCB load were measured in vitro during, respectively, tracking over single bend and during device insertion. Mean paclitaxel concentrations were equally high at ISR and naïve SFA treatment sites (56,984 vs. 79,837 ng/g, p > 0.99) and ranged from 9 to 89 ng/g in tissues downstream of these treatment sites. Sampling of non-target upstream iliac artery tissues revealed paclitaxel concentration of 4351 ± 4084 ng/g. Benchtop sliding of PCB samples onto ex vivo porcine artery samples exhibited efficient, pressure independent frictional paclitaxel transfer (124 µg at 0.05 atm vs 126 µg at 0.1 atm, p > 0.99). Conclusions: PCB interactions at porcine vessel bends led to premature tracking loss, resulting in peak plasma concentrations exceeding post-inflation concentrations, and delivery to upstream tissue that is plausibly explained as arising from efficient friction-mediated coating transfer.