A computational model of drug delivery through microcirculation to compare different tumor treatments
A computational model of drug delivery through microcirculation to compare different tumor treatments
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DOI：
10.1002/cnm.2661
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发表时间：
2014-11-01
影响因子：
2.1
通讯作者：
Zunino, P.
中科院分区：
文献类型：
--
作者：
Cattaneo, L.;Zunino, P.
从生物组织中过滤和运输的基本规律出发，我们开发了一个计算模型来捕获血液灌注，与间质体积的流体交换，毛细血管床中的质量运输，通过毛细血管壁并进入周围组织之间的相互作用。这些现象在微观水平上被解释，其中毛细血管和间隙体积被视为两个独立的区域。毛细血管被描述为运送血液流动的血管网络。我们将该模型应用于研究药物向肿瘤的递送。该模型可用于比较各种治疗方案。特别地，我们考虑使用药物推注和纳米颗粒注射到血流中的递送。该计算方法适用于治疗性能的系统量化，从而能够分析间质药物浓度水平、代谢速率和细胞存活分数。我们的研究表明，对于基于推注的治疗，药物剂量不能最佳地递送到肿瘤间质体积。使用纳米颗粒作为中间药物载体克服了以前递送方法的缺点。这项工作表明，所提出的理论和计算框架代表了一个有前途的工具，比较不同的癌症治疗的疗效。版权所有（c）2014约翰威利父子有限公司
Starting from the fundamental laws of filtration and transport in biological tissues, we develop a computational model to capture the interplay between blood perfusion, fluid exchange with the interstitial volume, mass transport in the capillary bed, through the capillary walls and into the surrounding tissue. These phenomena are accounted at the microscale level, where capillaries and interstitial volume are viewed as two separate regions. The capillaries are described as a network of vessels carrying blood flow. We apply the model to study drug delivery to tumors. The model can be adapted to compare various treatment options. In particular, we consider delivery using drug bolus injection and nanoparticle injection into the blood stream. The computational approach is suitable for a systematic quantification of the treatment performance, enabling the analysis of interstitial drug concentration levels, metabolization rates and cell surviving fractions. Our study suggests that for the treatment based on bolus injection, the drug dose is not optimally delivered to the tumor interstitial volume. Using nanoparticles as intermediate drug carriers overrides the shortcomings of the previous delivery approach. This work shows that the proposed theoretical and computational framework represents a promising tool to compare the efficacy of different cancer treatments. Copyright (c) 2014 John Wiley & Sons, Ltd.