使用基于生理学的药代动力学建模和模拟方法对纳米颗粒递送至肿瘤的荟萃分析。,ACS Nano

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使用基于生理学的药代动力学建模和模拟方法对纳米颗粒递送至肿瘤的荟萃分析。
ACS Nano ( IF 15.8 ) Pub Date : 2020-03-04 , DOI: 10.1021/acsnano.9b08142
Yi-Hsien Cheng _{1,

2} , Chunla He ₁ , Jim E Riviere _{1,

3} , Nancy A Monteiro-Riviere ₂ , Zhoumeng Lin _{1,

2}

Affiliation

许多研究都设计了具有不同理化特性的纳米颗粒，以提高实体瘤的递送效率，但根据一项使用非生理学方法的研究，平均和中值递送效率分别仅为注射剂量 (%ID) 的 1.48% 和 0.70%。基于 2005 年至 2015 年发布的数据的建模方法。在这项研究中，我们使用基于生理学的药代动力学 (PBPK) 模型分析了 376 个数据集，涵盖 2005 年至 2018 年发布的各种纳米药物，并发现了平均和中值递送效率最后采样时间点分别为 2.23% 和 0.76%ID。此外，静脉给药后，24 小时时的平均和中位递送效率分别为 2.24% 和 0.76%ID，168 小时时分别降至 1.23% 和 0.35%ID。虽然这些递送效率似乎高于以前的发现，但它们仍然相当低，并且是纳米药物临床转化的关键障碍。我们使用应用于金纳米粒子子集的更机械的 PBPK 视角来探索这种低递送效率的潜在原因，并发现低递送效率与肿瘤部位的低分布和渗透系数相关（P < 0.01）。我们还展示了如何将 PBPK 建模和模拟用作研究纳米药物的肿瘤递送效率的有效工具。

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Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach.

Numerous studies have engineered nanoparticles with different physicochemical properties to enhance the delivery efficiency to solid tumors, yet the mean and median delivery efficiencies are only 1.48% and 0.70% of the injected dose (%ID), respectively, according to a study using a nonphysiologically based modeling approach based on published data from 2005 to 2015. In this study, we used physiologically based pharmacokinetic (PBPK) models to analyze 376 data sets covering a wide range of nanomedicines published from 2005 to 2018 and found mean and median delivery efficiencies at the last sampling time point of 2.23% and 0.76%ID, respectively. Also, the mean and median delivery efficiencies were 2.24% and 0.76%ID at 24 h and were decreased to 1.23% and 0.35%ID at 168 h, respectively, after intravenous administration. While these delivery efficiencies appear to be higher than previous findings, they are still quite low and represent a critical barrier in the clinical translation of nanomedicines. We explored the potential causes of this poor delivery efficiency using the more mechanistic PBPK perspective applied to a subset of gold nanoparticles and found that low delivery efficiency was associated with low distribution and permeability coefficients at the tumor site (P < 0.01). We also demonstrate how PBPK modeling and simulation can be used as an effective tool to investigate tumor delivery efficiency of nanomedicines.

更新日期：2020-02-20

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