Marzieh K Atigh1, Emily Turner1, Uwe Christians2, Saami K Yazdani1. 1. Mechanical Engineering Department, University of South Alabama, Mobile, AL, USA. 2. iC42 Clinical Research and Development, University of Colorado, Aurora, CO, USA.
Abstract
AIM: Nonstent drug delivery platforms have recently emerged as an alternative treatment of peripheral arterial disease. Perfusion catheters have the potential to directly deliver antiproliferative agents to the medial arterial layer to prevent restenosis. The purpose of this study was to therefore determine the effectiveness of a perfusion catheter to deliver paclitaxel, a proven antiproliferative agent, to combat restenosis. METHODS: A benchtop model was utilized to determine the varying parameters of a novel occlusion perfusion catheter to maximize paclitaxel delivery using pharmacokinetic evaluation and fluorescent microscopy. Parameters tested included concentration of paclitaxel, delivery pressure, duration of delivery, and the use of an excipient. In addition, bilateral rabbit iliac arteries were treated with the perfusion catheter and pharmacokinetic evaluation performed at 1 hour, 1 day and 3 days. RESULTS: Benchtop testing demonstrated uniform and circumferential penetration of paclitaxel within the treated arteries. The results of the ex vivo test identified two groups with and without an excipient with similar loading conditions (with excipient: 15.4±8.6 ng/mg vs without excipient: 8.9±6.9 ng/mg, P=.77). The in vivo pharmacokinetic analysis of these two groups demonstrated the use of contrast agent increased arterial paclitaxel levels and maintained initial paclitaxel dosing up to 3 days (With excipient: 1 hour: 107±62 ng vs 3 days: 40±23 ng, P=.824; No excipient: 1 hour: 247±120 ng vs 3 days: 2.92±2.9 ng, P=.009). CONCLUSIONS: These results demonstrate the feasibility to deliver paclitaxel directly to the medial layer of an artery via a perfusion catheter.
AIM: Nonstent drug delivery platforms have recently emerged as an alternative treatment of peripheral arterial disease. Perfusion catheters have the potential to directly deliver antiproliferative agents to the medial arterial layer to prevent restenosis. The purpose of this study was to therefore determine the effectiveness of a perfusion catheter to deliver paclitaxel, a proven antiproliferative agent, to combat restenosis. METHODS: A benchtop model was utilized to determine the varying parameters of a novel occlusion perfusion catheter to maximize paclitaxel delivery using pharmacokinetic evaluation and fluorescent microscopy. Parameters tested included concentration of paclitaxel, delivery pressure, duration of delivery, and the use of an excipient. In addition, bilateral rabbit iliac arteries were treated with the perfusion catheter and pharmacokinetic evaluation performed at 1 hour, 1 day and 3 days. RESULTS: Benchtop testing demonstrated uniform and circumferential penetration of paclitaxel within the treated arteries. The results of the ex vivo test identified two groups with and without an excipient with similar loading conditions (with excipient: 15.4±8.6 ng/mg vs without excipient: 8.9±6.9 ng/mg, P=.77). The in vivo pharmacokinetic analysis of these two groups demonstrated the use of contrast agent increased arterial paclitaxel levels and maintained initial paclitaxel dosing up to 3 days (With excipient: 1 hour: 107±62 ng vs 3 days: 40±23 ng, P=.824; No excipient: 1 hour: 247±120 ng vs 3 days: 2.92±2.9 ng, P=.009). CONCLUSIONS: These results demonstrate the feasibility to deliver paclitaxel directly to the medial layer of an artery via a perfusion catheter.
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