Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-07-17 DOI:10.1016/j.nano.2024.102774

Oskar Axelsson PhD, Nooshin Yousefpour BSc, Olof Björnberg PhD, Erik Ekengard PhD, Sujinna Lekmeechai PhD

{"title":"Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01 clinical trial","authors":"Oskar Axelsson PhD, Nooshin Yousefpour BSc, Olof Björnberg PhD, Erik Ekengard PhD, Sujinna Lekmeechai PhD","doi":"10.1016/j.nano.2024.102774","DOIUrl":null,"url":null,"abstract":"<div><p>The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R<sup>2</sup> = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"62 ","pages":"Article 102774"},"PeriodicalIF":4.2000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000431/pdfft?md5=8601ad682c68920fc5432c9e86ab6def&pid=1-s2.0-S1549963424000431-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963424000431","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R² = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.

Abstract Image

查看原文本刊更多论文

尺寸依赖性肾过滤模型解释了功能纳米粒子的人体药代动力学：SPAGOPIX-01 临床试验。

病人服用基于纳米粒子的核磁共振成像造影剂 SN132D 后的药代动力学可以用与尺寸相关的清除机制来解释，并对这种行为进行了数值模拟。通过 ICP-OES 分析了 14 名患者血液样本中的硅（纳米粒子的一种成分）。药代动力学模型只有一个自由参数，依赖于造影剂的测量尺寸分布以及肾脏和心血管系统的既定特性。该模型与输注开始后十分钟到两周内的样本实验数据拟合良好（R2 = 0.9910）。这些结果支持人体肾脏过滤的截止直径为 5.5 纳米。实验与模型之间的一致性意味着血浆蛋白与纳米颗粒的结合很少或根本没有。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.