Drug Release Profiles of Different Drug-coated Balloon Platforms

Abstract

Drug-coated balloons are a new tool for the treatment of de novo or in-stent stenosis; as yet little is known about the principle by which these devices apply their therapeutic agents during intervention. Concerns remain regarding clinical safety and efficacy of different coatings, mainly influenced by the amount of drug transferred into the arterial tissue and lost into the bloodstream. To assess whether the chemical or mechanical set-up influences drug migration and wash-off, we compared four paclitaxel-coated balloon platforms differing in surface structure (folded versus non-folded) and coating compounds (pure paclitaxel versus paclitaxel plus excipient) in a porcine coronary model. The study revealed high wash-off rates for all devices, exceeding 54.4% of the initial coating contents. In terms of tissue concentration significant differences could be observed between the coating compounds independently from the device platform. For the paclitaxel versus paclitaxel plus excipient balloons tissue concentrations of 0.02 and 0.33μg/mm2, respectively (p<0.01), were detected; for the paclitaxel versus paclitaxel plus excipient-wrapped balloons tissue concentrations were 0.13 and 0.53μg/mm2, respectively (p=0.04). The main driver of drug migration from drug-coated balloon surfaces into arterial tissue is the chemical set-up of the coating. Hydrophilic excipients allow higher tissue concentrations of paclitaxel independent from the mechanical platform. The wash-off from the surface coating remains an unsolved safety issue and may be solved by mechanical modifications of these devices.

Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons

“…Most of these carriers are chosen on the basis of their usefulness to improve drug penetration into the tissue and not on whether they assist in delivering significant amount of drug at the treatment site of diseased portion of the artery. The major limitation of currently available DCBs is the delivery of drug from the balloons is not controlled effectively in order to avoid drug loss during balloon tracking and to rapidly deliver a therapeutic level of drug at the treatment site [11][12][13][14]. It has been reported that a significant amount of drug (up to 80%) is lost in the blood stream even before the balloon is tracked to the treatment site [11][12][13][14].…”

“…The major limitation of currently available DCBs is the delivery of drug from the balloons is not controlled effectively in order to avoid drug loss during balloon tracking and to rapidly deliver a therapeutic level of drug at the treatment site [11][12][13][14]. It has been reported that a significant amount of drug (up to 80%) is lost in the blood stream even before the balloon is tracked to the treatment site [11][12][13][14]. Also, during the short balloon inflation time (2 to 3 min), the drug is not rapidly transferred from the balloon to the tissue [11][12][13][14].…”

“…It has been reported that a significant amount of drug (up to 80%) is lost in the blood stream even before the balloon is tracked to the treatment site [11][12][13][14]. Also, during the short balloon inflation time (2 to 3 min), the drug is not rapidly transferred from the balloon to the tissue [11][12][13][14]. Hence, in many cases, only a subtherapeutic level of drug is delivered at the treatment site [11][12][13][14].…”

Endovascular Treatment with Drug-Coated Balloons in Femoropopliteal Artery Disease

“…Carriers, mostly hydrophilic structures, try to minimize the loss of the hydrophobic paclitaxel microparticles in the systemic circulation (19). The inflation time is as important as the efficacy of the carrier to reach therapeutic levels of paclitaxel in the target lesion (20).…”

Usage of different vessel models in a flow-through cell: in vitro study of a novel coated balloon catheter

“…25 Heilmann et al had found (via an in vivo study) that the advantageous effect of a hydrophilic additive such as using iopromide for higher tissue concentrations was antagonized by increased amounts of wash-off of used coatings. 26 Drug loss is a process constituted of mechanical loss by sheath passage and collisions with the vessel wall and dissolution of the coating in the blood stream. 26 This process will be simulated using a standard anatomic model adapted from ASTM F2394-07 (described in next section).…”