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

Autor:	Cooper K; Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States., Cawthon CV; Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States., Goel E; Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States., Atigh M; Mechanical Engineering Department, University of South Alabama, Mobile, AL, United States., Christians U; iC42 Clinical Research and Development, University of Colorado, Aurora, CO, United States., Yazdani SK; Department of Engineering, Wake Forest University, Winston-Salem, NC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in medical technology [Front Med Technol] 2021 Jun 10; Vol. 3, pp. 675188. Date of Electronic Publication: 2021 Jun 10 (Print Publication: 2021).
DOI:	10.3389/fmedt.2021.675188
Abstrakt:	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. Competing Interests: SY serves on the Scientific Advisory Board of Advanced Catheter and has received grant support from Advanced Catheter Therapies, Lutonix, Inc, Alucent Biomedical, Toray Industries and Biosensors International. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Cooper, Cawthon, Goel, Atigh, Christians and Yazdani.)
Databáze:	MEDLINE
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