纳米粒子生物分布系数：一种理解纳米颗粒组织分布的定量方法
Nanoparticle biodistribution coefficients: A quantitative approach for understanding the tissue distribution of nanoparticles
影响因子:17.60000
分区:医学1区 Top / 药学1区
发表日期:2023 Mar
作者:
Mokshada Kumar, Priyanka Kulkarni, Shufang Liu, Nagendra Chemuturi, Dhaval K Shah
摘要
该手稿的目的是为纳米颗粒的组织分布提供定量见解。从文献中收集了血浆，肿瘤和13种不同组织的纳米颗粒的药代动力学。使用纳米颗粒生物分布系数（NBC）对不同组织中的氧化石墨烯，脂质，聚合物，氧化铁和金纳米颗粒的生物分布进行了分析，并分析了2018年的数据集。观察到，通常在静脉内给药后，大多数纳米颗粒在肝脏中积累（NBC = 17.56％ID/g）和脾脏（NBC = 12.1％ID/g），而其他组织则获得了小于5％的ID/g。 NBC values for kidney, lungs, heart, bones, brain, stomach, intestine, pancreas, skin, muscle and tumor were found to be 3.1 %ID/g, 2.8 %ID/g, 1.8 %ID/g, 0.9 %ID/g, 0.3 %ID/g, 1.2 %ID/g, 1.8 %ID/g, 1.2 %ID/g, 1.0 %ID/g, 0.6 %ID/g and 3.4 %ID/g, 分别。在肝，脾脏和肺等某些器官中观察到纳米颗粒分布的显着差异。可以通过考虑纳米颗粒物理化学特性（例如大小和材料）的差异来解释这种变异性的很大一部分。提供了基于生理的纳米颗粒生理药代动力学（PBPK）模型的批判性概述，并且还讨论了我们当前有关体外和体内药代动力学知识的局限性，这些纳米颗粒限制了限制了强大的PBPK模型的发展。假设纳米颗粒的全身药代动力学以及可以预测其处置的数学模型的开发可以提高这些模式的成功临床翻译的可能性。
Abstract
The objective of this manuscript is to provide quantitative insights into the tissue distribution of nanoparticles. Published pharmacokinetics of nanoparticles in plasma, tumor and 13 different tissues of mice were collected from literature. A total of 2018 datasets were analyzed and biodistribution of graphene oxide, lipid, polymeric, silica, iron oxide and gold nanoparticles in different tissues was quantitatively characterized using Nanoparticle Biodistribution Coefficients (NBC). It was observed that typically after intravenous administration most of the nanoparticles are accumulated in the liver (NBC = 17.56 %ID/g) and spleen (NBC = 12.1 %ID/g), while other tissues received less than 5 %ID/g. NBC values for kidney, lungs, heart, bones, brain, stomach, intestine, pancreas, skin, muscle and tumor were found to be 3.1 %ID/g, 2.8 %ID/g, 1.8 %ID/g, 0.9 %ID/g, 0.3 %ID/g, 1.2 %ID/g, 1.8 %ID/g, 1.2 %ID/g, 1.0 %ID/g, 0.6 %ID/g and 3.4 %ID/g, respectively. Significant variability in nanoparticle distribution was observed in certain organs such as liver, spleen and lungs. A large fraction of this variability could be explained by accounting for the differences in nanoparticle physicochemical properties such as size and material. A critical overview of published nanoparticle physiologically-based pharmacokinetic (PBPK) models is provided, and limitations in our current knowledge about in vitro and in vivo pharmacokinetics of nanoparticles that restrict the development of robust PBPK models is also discussed. It is hypothesized that robust quantitative assessment of whole-body pharmacokinetics of nanoparticles and development of mathematical models that can predict their disposition can improve the probability of successful clinical translation of these modalities.