A mathematical model for predicting drug release from a biodurable drug-eluting stent coating
A mathematical model for predicting drug release from a biodurable drug-eluting stent coating
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DOI：
10.1002/jbm.a.31787
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发表时间：
2008-11-01
影响因子：
4.9
通讯作者：
Prabhu, Santosh
中科院分区：
文献类型：
--
作者：
Hossainy, Syed;Prabhu, Santosh
药物洗脱支架（DES）是已经商业化并被证明在治疗冠状动脉疾病方面安全有效的药物-器械组合产品。它们在降低新生内膜增生程度方面非常有效，因此可以预防或最大限度地减少支架内再狭窄的发生。为了开发成功的DES，必须将涂层设计成在支架植入后在动脉阻塞部位递送治疗剂量的药物持续所需的持续时间。数学模型是非常有价值的工具，可用于研究不同涂层参数对药物递送的影响，因此可以帮助涂层设计。我们已经开发了一个双峰集总参数质量传输模型来描述药物依维莫司从生物耐久性含氟聚合物的DES涂层的释放。我们假设，分散的药物相有助于两个离散的药物转运模式通过涂层。它们是快速模式（模式1）和缓慢模式（模式1），快速模式是药物从聚合物内药物相的高度包封结构中释放，缓慢模式是药物从涂层内药物的非包封的聚合物包封相中释放。描述模型的控制方程中的三个系数，即对应于两种模式中的每一种的两个有效扩散率和两种模式之一中的药物分数，通过与可用的DES释放数据拟合来确定。该模型的预测能力证明了从不同的涂层配置（厚度和药物聚合物的比例）与实验数据的释放速率进行比较。此外，它表明，如果有限的实验数据可在早期的时间点，该模型可用于预测在随后的时间点的药物释放。(c)2008 Wiley Periodicals，Inc.
Drug-eluting stents (DESs) are drug-device combination products that have been commercialized and demonstrated to be safe and efficacious in treating coronary artery disease. They have been very effective in reducing the extent of neointimal hyperplasia and therefore in preventing or minimizing the occurrence of in-stent restenosis. In order to develop a successful DES, it is imperative that the coating be designed so as to deliver, after stent implantation, a therapeutic dose of the drug for the desired time duration at the site of the arterial blockage. Mathematical models are very valuable tools that can be used to study the effect of different coating parameters on drug delivery and can therefore help in coating design. We have developed a bimodal lumped-para meter mass transport model to describe the release of the drug everolimus from a biodurable fluoropolymer-based DES coating. We assume that the dispersed drug phase contributes to two discrete modes of drug transport through the coating. These are the fast mode (mode 1) which is the release of the drug from a highly percolated structure of drug phase within the polymer, and the slow mode (mode 1) which is the release of the drug from a nonpercolated, polymer-encapsulated phase of the drug within the coating. The three coefficients in the governing equations describing the model, i.e. the two effective diffusivities corresponding to each of the two modes and the fraction of the drug in one of the two modes, were determined by fitting with available DES release data. The predictive power of the model is demonstrated by comparing the release rate from different coating configurations (thickness and drug to polymer ratios) with experimental data. Also, it is demonstrated that if limited experimental data are available at early time points, the model can be used to predict drug release at subsequent time points. (c) 2008 Wiley Periodicals, Inc.