Pulmonary delivery of siRNA-loaded lipid-polymer hybrid nanoparticles: Effect of nanoparticle size

Q2 Pharmacology, Toxicology and Pharmaceutics OpenNano Pub Date : 2023-09-01 DOI:10.1016/j.onano.2023.100180

Abishek Wadhwa , Thomas R. Bobak , Lennart Bohrmann , Reka Geczy , Sathiya Sekar , Gowtham Sathyanarayanan , Jörg P. Kutter , Henrik Franzyk , Camilla Foged , Katayoun Saatchi , Urs O. Häfeli

{"title":"Pulmonary delivery of siRNA-loaded lipid-polymer hybrid nanoparticles: Effect of nanoparticle size","authors":"Abishek Wadhwa , Thomas R. Bobak , Lennart Bohrmann , Reka Geczy , Sathiya Sekar , Gowtham Sathyanarayanan , Jörg P. Kutter , Henrik Franzyk , Camilla Foged , Katayoun Saatchi , Urs O. Häfeli","doi":"10.1016/j.onano.2023.100180","DOIUrl":null,"url":null,"abstract":"<div><p>Nanomedicines based on nanoparticles rely both on the potency of the drug as well as the efficiency of the delivery system, for which particle size plays a crucial role. For the intracellular delivery of small interference RNA (siRNA), lipid-polymer nanoparticle (LPN) hybrid systems constitute a safe and highly effective class of delivery systems. In the present study, we employ a microfluidics method for the manufacturing of spherical siRNA-loaded LPNs for pulmonary delivery with distinct size distributions with average diameters of approximately 70, 110, and 220 nm. We designed an optically clear, inexpensive thiol-ene polymeric microfluidic chip prototype that is compatible with standard ‘soft-lithography’ techniques, allows for replica molding, and is resistant to harsh solvents. By using SPECT/CT in vivo imaging, we show comparable pulmonary clearance patterns of all three differently sized LPN formulations following intratracheal administration. Also, negligible accumulation in the liver was observed.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"13 ","pages":"Article 100180"},"PeriodicalIF":0.0000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"OpenNano","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352952023000592","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}

引用次数: 0

Abstract

Nanomedicines based on nanoparticles rely both on the potency of the drug as well as the efficiency of the delivery system, for which particle size plays a crucial role. For the intracellular delivery of small interference RNA (siRNA), lipid-polymer nanoparticle (LPN) hybrid systems constitute a safe and highly effective class of delivery systems. In the present study, we employ a microfluidics method for the manufacturing of spherical siRNA-loaded LPNs for pulmonary delivery with distinct size distributions with average diameters of approximately 70, 110, and 220 nm. We designed an optically clear, inexpensive thiol-ene polymeric microfluidic chip prototype that is compatible with standard ‘soft-lithography’ techniques, allows for replica molding, and is resistant to harsh solvents. By using SPECT/CT in vivo imaging, we show comparable pulmonary clearance patterns of all three differently sized LPN formulations following intratracheal administration. Also, negligible accumulation in the liver was observed.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

sirna负载的脂质-聚合物混合纳米颗粒的肺递送:纳米颗粒大小的影响

基于纳米颗粒的纳米药物既依赖于药物的效力，也依赖于输送系统的效率，其中颗粒大小起着至关重要的作用。对于小干扰RNA (siRNA)的细胞内递送，脂质-聚合物纳米颗粒(LPN)混合系统构成了一种安全高效的递送系统。在本研究中，我们采用微流体方法制造了用于肺输送的球形sirna负载lpn，其平均直径约为70、110和220 nm。我们设计了一种光学清晰，廉价的巯基聚合物微流控芯片原型，它与标准的“软光刻”技术兼容，允许复制成型，并且耐苛刻的溶剂。通过使用SPECT/CT体内成像，我们显示了气管内给药后所有三种不同大小的LPN制剂的可比较的肺清除率模式。此外，在肝脏中观察到可忽略不计的积累。

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分钟内获得全文去求助

来源期刊

OpenNano Medicine-Pharmacology (medical)

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

50 days

期刊介绍： OpenNano is an internationally peer-reviewed and open access journal publishing high-quality review articles and original research papers on the burgeoning area of nanopharmaceutics and nanosized delivery systems for drugs, genes, and imaging agents. The Journal publishes basic, translational and clinical research as well as methodological papers and aims to bring together chemists, biochemists, cell biologists, material scientists, pharmaceutical scientists, pharmacologists, clinicians and all others working in this exciting and challenging area.