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

Frontiers in Medical Technology

卷:3

Saami K. Yazdani¹  Marzieh Atigh²  Claire V. Cawthon²  Emily Goel²  Kathryn Cooper²  Uwe Christians³ 

[1] Department of Engineering, Wake Forest University, Winston-Salem, NC, United States;

[2] Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States;

[3] iC42 Clinical Research and Development, University of Colorado, Aurora, CO, United States;

关键词: ex vivo;    methods;    pharmacokinetics;    interventional devices;    drug delivery;    paclitaxel;   

DOI  :  10.3389/fmedt.2021.675188

来源: DOAJ

【 摘 要 】

Purpose: The goal of this study was to develop an ex vivo system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries.Methods: A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The ex vivo bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our ex vivo 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 ex vivo measurements.Results: 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 ex vivo system. Similar results were measured in vivo, 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 ex vivo vs. in vivo.Conclusion: This system represents the first validated ex vivo 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.

【 授权许可】

Unknown