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

Kathryn Cooper; Claire V Cawthon; Emily Goel; Marzieh Atigh; Uwe Christians; Saami K Yazdani

doi:10.3389/fmedt.2021.675188

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

Front Med Technol. 2021 Jun 10:3:675188. doi: 10.3389/fmedt.2021.675188. eCollection 2021.

Authors

Kathryn Cooper¹, Claire V Cawthon¹, Emily Goel¹, Marzieh Atigh¹, Uwe Christians², Saami K Yazdani³

Affiliations

¹ Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States.
² iC42 Clinical Research and Development, University of Colorado, Aurora, CO, United States.
³ Department of Engineering, Wake Forest University, Winston-Salem, NC, United States.

Abstract

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.

Keywords: drug coated balloon; drug delivery; ex vivo; interventional devices; methods; paclitaxel; pharmacokinetics.

Abstract

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