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

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.

Syndecan‐4 and stromal cell‐derived factor‐1 alpha functionalized endovascular scaffold facilitates adhesion, spreading and differentiation of endothelial colony forming cells and functions under flow and shear stress conditions

“…To determine if the SDF‐1 bound on PFC was resilient to vascular flow and pressure, conduits of the appropriate size of vessels that typically used in CABG surgeries were fabricated using fPFC. These conduits were tested in a custom‐built bioreactor 32 . The initial ID of fPFC conduit was 4 mm.…”

“…The flow medium was saline with 1% antibiotic‐antimycotic from Gibco (Waltham, Massachusetts). A custom LabVIEW program was used to generate the flow waveform and to control and monitor the flow and pressure within the bioreactor system 32 . The ID of fPFC vascular conduits was measured using a Chison ECO5 Portable Ultrasound immediately after the flow was started and at 1, 3, 6, and 24 h. After the flow cycle was complete, the vascular conduits were retrieved.…”

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

“… 22 , 24 , 28 , 29 However, in this study, we performed delivery procedures with varying parameters to evaluate the uptake of drug using a validated ex vivo model. 19 , 20 , 22 , 26 , 30 , 31 Transit time, a crucial procedural variable specific to DCB, was one of the variables evaluated. We selected to compare a transit time of 30 seconds versus 3 minutes as these are key time points identified by the manufacturer’s procedural guidelines.…”

“…22,24,28,29 However, in this study, we performed delivery procedures with varying parameters to evaluate the uptake of drug using a validated ex vivo model. 19,20,22,26,30,31 Transit time, a crucial procedural variable specific to DCB, was one of the variables evaluated. We The results of our ex vivo model supports previous in vivo studies showing significant drug loss of DCB coating in a prolonged aqueous environment.…”

“…12,18 To date, pre-clinical models have served as the primary process to evaluate and quantify DCB delivery outcomes. 15,[19][20][21][22][23][24][25] The objective of this study is to implement a bench-top system to optimize DCB drug transfer. Specifically, we investigated the impact of various transit time and balloon-to-artery ratios on acute drug transfer and retention in an ex vivo flow circuit using harvested porcine carotid arteries.…”