Assessing the influence of atherosclerosis on drug coated balloon therapy using computational modelling

Anbalakan, Karthic; Toh, Han Wei; Ang, Hui Ying; Buist, Martin L.; Leo, Hwa Liang

doi:10.1016/j.ejpb.2020.09.016

Cited by 10 publications

(15 citation statements)

References 28 publications

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“…Furthermore, compared to other anatomical locations, DCB inflation in SFAs may be prolonged for several minutes [ 35 ]. In accordance with the recent findings for 2D cross-sectional diseased coronary arteries [ 15 ], the longer the DCB application, the deeper the penetration front within the tissue. Moreover, the introduction of the behavior of the paclitaxel within the intracellular environment through specific binding provides interesting insights coherent with previous experimental findings [ 36 ], in which paclitaxel retention remained particularly high in the first hour after DCB implantation.…”

Section: Discussionsupporting

confidence: 92%

“…From the findings on the impact of different tissue composition on drug transport, and in accordance with previous literature on DCB computational modelling [ 15 , 16 , 18 ], marked differences in terms of free and bound concentrations were found between the regions Ω HEAL and Ω CALC . These results reflected the difference in terms of effective drug diffusivity, which was 4 orders of magnitude lower in the diseased region than in the healthy one, and the lower maximum binding sites density [ 21 ].…”

Section: Discussionsupporting

confidence: 88%

“…In contrast to the vast literature considering computational modeling of the drug eluting stents (e.g. [ 28 , 31 – 33 ]), where drug delivery is typically sustained over a period of weeks, the number of published studies considering computational modeling of DCBs (and specifically for diseased SFAs) is extremely low [ 15 – 18 ]. Given the limited time of contact between the DCB external surface and the arterial wall, an adequate understanding of drug transport and retention in a realistic arterial model and of the impact of procedural aspects becomes of extreme importance for the success of DCB treatment for diseased SFAs [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fig 2 shows a schematic representation of the biological processes and current understanding of the action of paclitaxel. Only the reversible and saturable specific binding was integrated in this model, neglecting the non-specific binding of paclitaxel (namely the binding of the paclitaxel molecule to various extracellular matrix components [ 15 ]). This is biologically translated into the exertion of the effect (i.e.…”

Section: Methodsmentioning

confidence: 99%

“…Through the inclusion of a reaction term within the governing drug transport equations, computational models provide insights into paclitaxel uptake and release with a level of detail difficult or impossible to replicate with in-vitro or in-vivo methods. Despite the usefulness of computational methodology to assess the safety and the performance of DCBs, to date only a few studies have considered drug transport following release from DCBs [ 15 – 18 ] and only one of these has focused on its application in SFAs. Furthermore, all of these studies are inherently limited by their consideration of a highly-simplified two-dimensional (2D) vessel geometry.…”

Section: Introductionmentioning

confidence: 99%

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3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

et al. 2021

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Background/Objectives Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry. Methods An idealized three-dimensional model of a superficial femoral artery presenting with a calcific plaque and treated with a drug-coated balloon was created to perform transient mass transport simulations. To account for the transport of drug (i.e. paclitaxel) released by the device, a diffusion-reaction equation was implemented by describing the drug bound to specific intracellular receptors through a non-linear, reversible reaction. The following features concerning procedural aspects, pathologies and modelling assumptions were investigated: (i) balloon application time (60–180 seconds); (ii) vessel wall composition (healthy vs. calcified wall); (iii) sequential balloon application; and (iv) drug wash-out by the blood stream vs. coating retention, modeled as exponential decay. Results The balloon inflation time impacted both the free and specifically-bound drug concentrations in the vessel wall. The vessel wall composition highly affected the drug concentrations. In particular, the specifically-bound drug concentration was four orders of magnitude lower in the calcific compared with healthy vessel wall portions, primarily as a result of reduced drug diffusion. The sequential application of two drug-coated balloons led to modest differences (~15%) in drug concentration immediately after inflation, which became negligible within 10 minutes. The retention of the balloon coating increased the drug concentration in the vessel wall fourfold. Conclusions The overall findings suggest that paclitaxel kinetics may be affected not only by the geometrical and compositional features of the vessel treated with the drug-coated balloon, but also by balloon design characteristics and procedural aspects that should be carefully considered.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

et al. 2021

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Understudied factors in drug‐coated balloon design and evaluation: A biophysical perspective

Shazly

Torres

Secemsky

et al. 2022

Bioengineering & Transla Med

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Drug‐coated balloon (DCB) percutaneous interventional therapy allows for durable reopening of the narrowed lumen via physical tissue expansion and local anti‐restenosis drug delivery, providing an alternative to traditional uncoated balloons or a permanent indwelling implant such as a conventional metallic drug‐eluting stent. While DCB‐based treatment of peripheral arterial disease (PAD) has been incorporated into clinical guidelines, DCB use has been recently curtailed due to reports that showed evidence of increased mortality risk in patients treated with paclitaxel (PTX)‐coated balloons. Given the United States Food and Drug Administration's 2019 consequent warning regarding PTX‐eluting DCBs and the subsequent marked reduction in clinical DCB use, there is now a critical need to better understand the compositional and mechanical factors underlying DCB efficacy and safety. Most work to date on DCB refinement has focused on designing both the enabling balloon catheter and alternate coatings composed of various drugs and excipients, followed by device evaluation in preclinical and clinical studies. We contend that improvement in DCB performance will require a better understanding of the biophysical factors operative during and following balloon deployment, and moreover that the elaboration and demonstrated control of these factors are needed to address current concerns with DCB use. This article provides a perspective on the biophysical interactions that govern DCB performance and offers new design strategies for the development of next‐generation DCB devices.

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How does the Nature of an Excipient and an Atheroma Influence Drug-Coated Balloon Therapy?

Anbalakan

Toh

Ang

et al. 2022

Cardiovasc Eng Tech

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Assessing the influence of atherosclerosis on drug coated balloon therapy using computational modelling

Cited by 10 publications

References 28 publications

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries

Understudied factors in drug‐coated balloon design and evaluation: A biophysical perspective

How does the Nature of an Excipient and an Atheroma Influence Drug-Coated Balloon Therapy?

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