Pre-Clinical Investigation of Liquid Paclitaxel for Local Drug Delivery: A Pilot Study

Cawthon, Claire V.; Cooper, Kathryn; Huett, Clifton; Lloret, Alyssa; Villar-Matamoros, Estefanny; Stokes, Lauren; Christians, Uwe; Schuler, Michele A.; Yazdani, Saami K.

doi:10.3390/ph13120434

Cited by 4 publications

(9 citation statements)

References 27 publications

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“… 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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…The treated region, along with residual paclitaxel content on the balloons, were evaluated by a validated high-performance liquid chromatography (HPLC) electrospray Ionization-tandem, as previously described. 20 , 22 , 26 …”

Section: Methodsmentioning

confidence: 99%

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

Villar-Matamoros

Stokes

Lloret

et al. 2022

J Cardiovasc Pharmacol Ther

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Objective: The purpose of this study was to determine the impact of varying inflation parameters on paclitaxel delivery and retention using a commercially available DCB. Background: Drug-coated balloons (DCB) have become the standard treatment for peripheral artery disease. Clinical data suggest that varying DCB delivery parameters directly impact patient outcome. Differences in delivery parameters can potentially alter the retention of the drug coating on DCBs. Methods: Harvested porcine carotid arteries were utilized in an ex vivo pulsatile flow bioreactor system. The DCBs were then deployed at a DCB-to-artery ratio of 1:1 or 1.25:1, an inflation time of 30 seconds or 1 minute and transit time of 30 seconds or 3 minutes. The amount of drug retention in arterial tissue was evaluated by pharmacokinetic analysis at 1 hour and 1 day post DCB deployment. Results: Arterial paclitaxel levels were found to be less at an inflation ratio of 1:1 with 3-minute transit time as compared to 30 seconds of transit time at 1 hour (12.3 ± 1.6 ng/mg vs. 391 ± 139 ng/mg, P = .036). At 1-day, DCBs deployed at a ratio of 1:1 resulted in less drug retention as compared to 1.25:1 (61.3 ± 23.1 ng/mg vs. 404 ± 195 ng/mg, P = .013). Conclusion: Arterial paclitaxel retention is reduced with extended transit times and sub-optimal expansion of the balloon. Optimization of delivery parameters can serve as an effective strategy to enhance clinical DCB outcomes.

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Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Villar-Matamoros

Stokes

Lloret

et al. 2022

J Cardiovasc Pharmacol Ther

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“…As the outer surface of the coated balloon comes in contact with the arterial wall, the drug and excipient are transferred onto the luminal surface of the artery. Paclitaxel has been the most widely used anti-proliferative drug used in all current FDA-approved DCBs 14 .Perfusion catheters are a new class of device that can locally administer drugs in liquid form within arteries to treat vascular disease [15][16][17] . The perfusion catheter is the ultimate leave nothing behind strategy for treating occlusive arterial disease.…”

mentioning

confidence: 99%

“…Perfusion catheters are a new class of device that can locally administer drugs in liquid form within arteries to treat vascular disease [15][16][17] . The perfusion catheter is the ultimate leave nothing behind strategy for treating occlusive arterial disease.…”

mentioning

confidence: 99%

Precision delivery of liquid therapy into the arterial wall for the treatment of peripheral arterial disease

Atigh

Goel

Erwin

et al. 2021

Sci Rep

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Perfusion catheters have recently emerged as a novel approach to deliver liquid anti-proliferative agents into flow obstructed arterial segments. The purpose of this study was to determine the impact of luminal delivery pressure on liquid drug penetration into the vessel wall. An ex vivo model using harvested porcine carotid arteries and a two-dimensional computational model were utilized to determine the impact of delivery pressure of liquid therapy into the arterial wall. A pig peripheral injury model determined the impact of intra-luminal delivery pressure on drug retention. Ex vivo results demonstrated that depth of fluid penetration varies from 6.93 ± 1.90% at 0 atm to 27.75 ± 6.61% penetration of the medial layer at 0.4 atm. Computational results had similar outcomes, as penetration varied between 4.4% and 22.84%. The in vivo results demonstrated significant increase in drug delivery to the arterial tissue at 0.4 atm versus 0.1 atm at 1 h (23.43 ± 13.59 ng/mg vs. 2.49 ± 1.81 ng/mg, p = 0.026) and 7 days (0.50 ± 0.39 ng/mg vs. 0.018 ± 0.023 ng/mg, p = 0.0496). The result of this study provides an innovative strategic and technical approach to enable targeted liquid therapy.

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Design and use of an ex vivo peripheral simulating bioreactor system for pharmacokinetic analysis of a drug coated stent

Chen,

Krinsky,

Phillips

et al. 2023

Bioengineering & Transla Med

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Currently, there are no ex vivo systems that can model the motion of peripheral arteries and allow for the evaluation of pharmacokinetics (PK) of endovascular devices. The objective of this study was to develop a novel peripheral simulating bioreactor system to evaluate drug pharmacokinetics of stents. We utilized 3D‐printed and off‐the‐shelf components to construct a peripheral‐simulating bioreactor system capable of mimicking the motion of peripheral arteries. Servo motors were primarily used to shorten/elongate, twist, and bend explanted porcine carotid arteries. To evaluate the pharmacokinetics in the bioreactor, drug‐eluting stents were deployed within explanted arteries and subjected to vascular motion along with pulsatile flow conditions. Following 30 min and 24 h, the arteries were removed, and paclitaxel levels were measured. Scanning electron microscopy was also performed to evaluate the stent surface. Arterial paclitaxel levels of the stent‐treated arteries were found to be higher at 30 min than at 24 h following pulsatile and no vascular motion and even higher at 24 h following pulsatile flow and vascular motion. The residual drug on the stent significantly decreased from 30 min to 24 h. Scanning electron microscopy confirmed the loss of paclitaxel coating at 24 h and greater disturbance in stents under peripheral motion versus pulsatile only. This system represents the first ex vivo system to determine the PK of drug‐eluting stents under physiological flow and vascular motion conditions. This work provides a novel system for a quick and inexpensive preclinical tool to study acute drug tissue concentration kinetics of drug‐releasing interventional vascular devices designed for peripheral applications.

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Pre-Clinical Investigation of Liquid Paclitaxel for Local Drug Delivery: A Pilot Study

Cited by 4 publications

References 27 publications

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

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

Precision delivery of liquid therapy into the arterial wall for the treatment of peripheral arterial disease

Design and use of an ex vivo peripheral simulating bioreactor system for pharmacokinetic analysis of a drug coated stent

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