The Development of an ex vivo Flow System to Assess Acute Arterial Drug Retention of Cardiovascular Intravascular Devices

• Published in: Frontiers in medical technology 2021-06, Vol.3, p.675188-675188
• Main Authors: Cooper, Kathryn, Cawthon, Claire V, Goel, Emily, Atigh, Marzieh, Christians, Uwe, Yazdani, Saami K
• Format: Article
• Language: English
• Subjects: drug delivery; ex vivo; interventional devices; Medical Technology; methods; paclitaxel; pharmacokinetics
• ISSN: 2673-3129; 2673-3129
• DOI: 10.3389/fmedt.2021.675188

The goal of this study was to develop an system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries. A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our system, a paclitaxel-coated balloon and a perfusion catheter device delivering liquid paclitaxel were utilized. At 1-h post-drug delivery, arteries were removed, and paclitaxel drug levels measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parallel experiments were performed in a pig model to validate measurements. LC-MS/MS analysis demonstrated arterial paclitaxel levels of the drug-coated balloon-treated arteries to be 48.49 ± 24.09 ng/mg and the perfusion catheter-treated arteries to be 25.42 ± 9.74 ng/mg at 1 h in the system. Similar results were measured , as arterial paclitaxel concentrations were measured at 59.23 ± 41.27 ng/mg for the drug-coated balloon-treated arteries and 23.43 ± 20.23 ng/mg for the perfusion catheter-treated arteries. Overall, no significant differences were observed between paclitaxel measurements of arteries treated vs. . This system represents the first validated pulsatile system to determine pharmacokinetics in a native blood vessel. This work provides proof-of-concept of a quick, inexpensive, preclinical tool to study acute drug tissue concentration kinetics of drug-releasing interventional vascular devices.