Differences and Similarities of the Intravenously Administered Lipid Nanoparticles in Three Clinical Trials: Potential Linkage between Lipid Nanoparticles and Extracellular Vesicles

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2023-09-17 DOI:10.1021/acs.molpharmaceut.3c00547

Yuta Suzuki*, Yuri Katsurada and Kenji Hyodo,

{"title":"Differences and Similarities of the Intravenously Administered Lipid Nanoparticles in Three Clinical Trials: Potential Linkage between Lipid Nanoparticles and Extracellular Vesicles","authors":"Yuta Suzuki*, Yuri Katsurada and Kenji Hyodo, ","doi":"10.1021/acs.molpharmaceut.3c00547","DOIUrl":null,"url":null,"abstract":"<p >Lipid nanoparticles (LNPs) are clinically validated drug-delivery carriers. However, clinical data on intravenously administered LNPs are limited compared with those on intramuscularly administered LNPs (mRNA vaccines against COVID-19). Here, we reviewed three clinically tested intravenously administered LNPs (patisiran, mRNA-1944, and NTLA-2001). We summarize the differences and similarities in their formulations, mechanisms of action, and pharmacokinetics profiles. In humans, patisiran and mRNA-1944 exhibited similar multiphasic pharmacokinetic profiles with a secondary peak in the RNA concentration. siRNA (patisiran) and mRNA (mRNA-1944) exhibited prolonged blood circulation and were detectable for more than 28 days after a single administration. We further summarize the basics of extracellular vesicles (EVs) and discuss the potential linkages between LNPs and EVs. This Review provides an understanding of the human clinical data of intravenous LNP formulations, which can be potentially explored to develop next-generation LNP-and EV-based drug delivery carriers.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"20 10","pages":"4883–4892"},"PeriodicalIF":4.5000,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00547","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

Lipid nanoparticles (LNPs) are clinically validated drug-delivery carriers. However, clinical data on intravenously administered LNPs are limited compared with those on intramuscularly administered LNPs (mRNA vaccines against COVID-19). Here, we reviewed three clinically tested intravenously administered LNPs (patisiran, mRNA-1944, and NTLA-2001). We summarize the differences and similarities in their formulations, mechanisms of action, and pharmacokinetics profiles. In humans, patisiran and mRNA-1944 exhibited similar multiphasic pharmacokinetic profiles with a secondary peak in the RNA concentration. siRNA (patisiran) and mRNA (mRNA-1944) exhibited prolonged blood circulation and were detectable for more than 28 days after a single administration. We further summarize the basics of extracellular vesicles (EVs) and discuss the potential linkages between LNPs and EVs. This Review provides an understanding of the human clinical data of intravenous LNP formulations, which can be potentially explored to develop next-generation LNP-and EV-based drug delivery carriers.

Abstract Image

查看原文本刊更多论文

三项临床试验中静脉注射脂质纳米颗粒的异同：脂质纳米颗粒和细胞外小泡之间的潜在联系

脂质纳米颗粒（LNPs）是经临床验证的药物递送载体。然而，与肌肉注射LNP（针对新冠肺炎的mRNA疫苗）相比，静脉注射LNP的临床数据有限。在此，我们回顾了三种经临床测试的静脉注射LNP（帕西兰、mRNA-1944和NTLA-2001）。我们总结了它们在配方、作用机制和药代动力学方面的异同。在人类中，帕西兰和mRNA-1944表现出相似的多相药代动力学特征，在RNA浓度中具有第二峰值。siRNA（patisiran）和mRNA（mRNA-1944）表现出延长的血液循环，并且在单次给药后可检测超过28天。我们进一步总结了细胞外小泡（EV）的基础知识，并讨论了LNPs和EV之间的潜在联系。这篇综述提供了对静脉注射LNP制剂的人类临床数据的理解，可用于开发下一代基于LNP和EV的药物递送载体。

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

Molecular Pharmaceutics 医学-药学

CiteScore

8.00

自引率

6.10%

发文量

391

审稿时长

2 months

期刊介绍： Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.