Understanding the Mechanism of Drug Transfer and Retention of Drug-Coated Balloons

Abstract

Objective: The purpose of this study was to determine the impact of varying inflation parameters on paclitaxel delivery and retention using a commercially available DCB. Background: Drug-coated balloons (DCB) have become the standard treatment for peripheral artery disease. Clinical data suggest that varying DCB delivery parameters directly impact patient outcome. Differences in delivery parameters can potentially alter the retention of the drug coating on DCBs. Methods: Harvested porcine carotid arteries were utilized in an ex vivo pulsatile flow bioreactor system. The DCBs were then deployed at a DCB-to-artery ratio of 1:1 or 1.25:1, an inflation time of 30 seconds or 1 minute and transit time of 30 seconds or 3 minutes. The amount of drug retention in arterial tissue was evaluated by pharmacokinetic analysis at 1 hour and 1 day post DCB deployment. Results: Arterial paclitaxel levels were found to be less at an inflation ratio of 1:1 with 3-minute transit time as compared to 30 seconds of transit time at 1 hour (12.3 ± 1.6 ng/mg vs. 391 ± 139 ng/mg, P = .036). At 1-day, DCBs deployed at a ratio of 1:1 resulted in less drug retention as compared to 1.25:1 (61.3 ± 23.1 ng/mg vs. 404 ± 195 ng/mg, P = .013). Conclusion: Arterial paclitaxel retention is reduced with extended transit times and sub-optimal expansion of the balloon. Optimization of delivery parameters can serve as an effective strategy to enhance clinical DCB outcomes.

Design and use of an ex vivo peripheral simulating bioreactor system for pharmacokinetic analysis of a drug coated stent

“…Paclitaxel stent and tissue concentrations were quantified using a validated, previously described high‐performance liquid chromatography (HPLC)‐electrospray ionization–tandem mass spectrometry system assay (LC–MS/MS) 25–27 …”

“…Paclitaxel stent and tissue concentrations were quantified using a validated, previously described high-performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry system assay (LC-MS/MS). [25][26][27] To visualize the stent surface following deployment, the 30-min and 24-h treated stents were fixed with 10% formalin and dehydrated in a graded series of ethanol. After critical point drying, the tissue samples were mounted and sputter-coated with gold.…”

Pre-clinical investigation of liquid sirolimus for local drug delivery

“…The arteries were cut to lengths ranging from approximately 5–8 cm and stored in 15 ml centrifuge tubes at −20°C until needed. As described previously ( 8 , 9 ), the ex vivo bioreactor system used in this study consisted of a flow reservoir, pump, vessel housing compartment, and distal flow constructor ( Figure 1 ). The pressure was monitored by using a catheter pressure transducer (Millar Instruments, Houston, TX, USA).…”