Laboratory of Biological Structure Mechanics (LaBS), Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy.
Malcom Randall VAMC, Gainesville, Florida, United States of America.
PLoS One. 2021 Oct 11;16(10):e0256783. doi: 10.1371/journal.pone.0256783. eCollection 2021.
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.
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.
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.
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.
背景/目的：药物涂层球囊治疗病变的股浅动脉仍然存在争议。尽管具有临床相关性，但迄今为止，仅提出了一些基于简单二维模型的计算研究来对此种血管内治疗进行研究。通过在三维几何形状中分析药物涂层球囊扩张过程中发生的药物输送和动力学，本工作解决了上述局限性。
创建了一个理想化的伴有钙化斑块的股浅动脉的三维模型，并用药物涂层球囊进行治疗，以进行瞬态质量传输模拟。为了考虑药物（即紫杉醇）通过设备释放的输送，通过描述药物与特定细胞内受体通过非线性、可逆反应结合的扩散-反应方程来实现。研究了与程序方面、病理学和建模假设相关的以下特征：（i）球囊应用时间（60-180 秒）；（ii）血管壁组成（健康与钙化壁）；（iii）球囊顺序应用；（iv）药物通过血流冲洗与涂层保留，模拟为指数衰减。
球囊膨胀时间会影响血管壁中游离和特异性结合的药物浓度。血管壁组成会极大地影响药物浓度。特别是，与健康血管壁部分相比，钙化血管壁部分的特异性结合药物浓度低四个数量级，主要是由于药物扩散减少。两个药物涂层球囊的顺序应用会导致膨胀后立即的药物浓度略有差异（约 15%），10 分钟内则变得可以忽略不计。球囊涂层的保留会使血管壁中的药物浓度增加四倍。
总体发现表明，紫杉醇动力学不仅受药物涂层球囊治疗的血管的几何形状和组成特征影响，还受球囊设计特征和程序方面的影响，这些因素应仔细考虑。
