Mathematical modeling of the receptor-mediated endocytosis process of targeted therapeutic agents in drug delivery systems
Mathematical modeling of the receptor-mediated endocytosis process of targeted therapeutic agents in drug delivery systems
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DOI：
10.1016/j.apm.2019.10.037
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发表时间：
2020-03-01
影响因子：
5
通讯作者：
Jung, Il Hyo
中科院分区：
文献类型：
--
作者：
Byun, Jong Hyuk;Jung, Il Hyo
在本文中，我们提出了描述受体介导的内吞作用过程的数学模型。一种是关于药物-靶标结合过程的随机微分模型。评估了平均消光时间和随时间分布的标准变化。另一种是年龄结构的模型，用于展示内吞作用和溶酶体过程。靶向给药系统有一个复杂的过程，它如何将药物分子在给药、血液和跨膜运输到细胞内空间以及抑制微管聚合方面进行传递。特别是，受体介导的靶向治疗药物的内吞作用，如抗体药物结合物或配体靶向脂质体包裹的纳米颗粒，是理解药物传递机制的关键一步。我们讨论了当智能体-靶复合体与自由智能体相比变化不明显时的随机准稳态近似。这减少了系统的数量和参数；但是，无法捕获初始时间段。此外，我们还讨论了与考虑内吞作用和溶酶体过程的完整模型相比，年龄结构模型引入简化模型的优点和缺点。如果直到有效载荷在细胞内释放的总平均保留时间已知，则具有Erlang分布的年龄结构模型可以用更少的参数很好地预测释放的有效载荷随时间分布的数据；然而，诱导间隔失去了它们的物理意义，并且只描述了延迟。(C)2019 Elsevier Inc.保留所有权利。
In this paper, we propose mathematical models to describe receptor-mediated endocytosis processes. One is a stochastic differential model for the agent-target binding process. The mean extinction time and a standard variation over time profile are evaluated. The other is an age-structured model for demonstrating endocytosis and lysosome processes. A targeted drug delivery system has a complex process in how it is to deliver drug molecules in terms of administration, transportation in blood and across membranes to intracellular space, and inhibition to microtubule polymerization. In particular, receptor-mediated endocytosis of targeted therapeutic agents, such as antibody drug conjugates or ligand-targeted liposome encapsulated nanoparticles, is a key step in understanding the drug delivery mechanism. We discuss stochastic quasi steady state approximation when agent-target complex does not appreciably vary compared with the free agents. This reduces the number of the systems and the parameters; however, an initial time phase cannot be captured. In addition, we discuss the strengths and weaknesses when the age-structured model induces the reduced model compared with the full model that considers endocytosis and lysosome processes. If the total mean retention time until payload release in intracellular space is known, then the age-structured model with the Erlang distribution may fairly predict data of the released payload over time profile with far fewer parameters; however, induced compartments lose their physical meaning and describe only a delay. (C) 2019 Elsevier Inc. All rights reserved.