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一种通过微循环进行药物递送以比较不同肿瘤治疗方法的计算模型。

A computational model of drug delivery through microcirculation to compare different tumor treatments.

作者信息

Cattaneo L, Zunino P

机构信息

MOX, Department of Mathematics "Francesco Brioschi", Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milano, Italy.

出版信息

Int J Numer Method Biomed Eng. 2014 Nov;30(11):1347-71. doi: 10.1002/cnm.2661. Epub 2014 Jul 31.

Abstract

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.

摘要

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,以捕捉血液灌注、与组织间隙体积的液体交换、毛细血管床中的物质运输、通过毛细血管壁并进入周围组织之间的相互作用。这些现象在微观层面上进行考虑,其中毛细血管和组织间隙体积被视为两个独立的区域。毛细血管被描述为一个携带血流的血管网络。我们应用该模型来研究药物向肿瘤的递送。该模型可用于比较各种治疗方案。特别是,我们考虑通过将药物推注注射和纳米颗粒注射到血流中来进行递送。这种计算方法适用于对治疗性能进行系统量化,能够分析组织间隙药物浓度水平、代谢率和细胞存活分数。我们的研究表明,对于基于推注注射的治疗,药物剂量并未最优地递送至肿瘤组织间隙体积。使用纳米颗粒作为中间药物载体克服了先前递送方法的缺点。这项工作表明,所提出的理论和计算框架是比较不同癌症治疗效果的一个有前景的工具。

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