A mathematical model to predict nanomedicine pharmacokinetics and tumor delivery
A mathematical model to predict nanomedicine pharmacokinetics and tumor delivery
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DOI：
10.1016/j.csbj.2020.02.014
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发表时间：
2020-01-01
影响因子：
6
通讯作者：
Wang, Zhihui
中科院分区：
文献类型：
--
作者：
Dogra, Prashant;Butner, Joseph D.;Wang, Zhihui
对于癌症纳米药物的临床翻译，系统地研究与纳米粒子的物理化学性质、肿瘤特性和个体差异有关的各种参数对治疗性纳米材料的肿瘤递送效率具有重要意义。由于参数空间巨大，使用传统的实验方法对这些参数进行全面研究是不切实际的；数学模型提供了一种在这样一个多维空间中导航的更容易处理的方法。为此，我们建立了NP体内药代动力学和肿瘤给药的预测数学模型，并进行了局部和全局的敏感性分析，以确定导致肿瘤给药效率低和NPs在靶外积累高的因素。我们的分析表明，NP降解率、肿瘤血液粘度、NP大小、肿瘤血管分数和肿瘤血管孔隙率是控制肿瘤间质中NP动力学的关键参数。讨论了这些参数对NPs肿瘤递送效率的影响，并给出了最大化NP递送的最佳值。(C)2020作者。由Elsevier B.V.代表计算和结构生物技术研究网络出版。
Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parameters using traditional experimental approaches is impractical due to the vast parameter space; mathematical models provide a more tractable approach to navigate through such a multidimensional space. To this end, we have developed a predictive mathematical model of whole-body NP pharmacokinetics and their tumor delivery in vivo, and have conducted local and global sensitivity analyses to identify the factors that result in low tumor delivery efficiency and high off-target accumulation of NPs. Our analyses reveal that NP degradation rate, tumor blood viscosity, NP size, tumor vascular fraction, and tumor vascular porosity are the key parameters in governing NP kinetics in the tumor interstitium. The impact of these parameters on tumor delivery efficiency of NPs is discussed, and optimal values for maximizing NP delivery are presented. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.