DataVXACS Applied Materials & InterfacesPaper
journal article·2025-02-26Open access

Nebulization of RNA-Loaded Micelle-Embedded Polyplexes as a Potential Treatment of Idiopathic Pulmonary Fibrosis

Joschka T. Müller, Adrian P. E. Kromer, Aysan Ezaddoustdar, Ioannis Alexopoulos, Katharina M. Steinegger, Diana Leidy Porras-Gonzalez, Otto Berninghausen, Roland Beckmann, Peter Braubach, Gerald Burgstaller, Malgorzata Wygrecka, Olivia M. Merkel

ACS Applied Materials & Interfaces· Volume 17· Issue 8
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Abstract

High Resolution Image Download MS PowerPoint Slide Biodegradable poly(β-amino) esters (PBAEs) have been a focus of interest for delivering therapeutic siRNA for several years. While no approved therapies are on the market yet, our study aims to advance PBAE-based treatments for currently “undruggable” diseases. The PBAEs used in this study are based on a recently reported step-growth copolymerization, which results in polymers with a unique balance of lipophilicity and positive charge, thereby showcasing diverse properties. Upon incubation with siRNA, these PBAEs form a unique structure and topology, which we classify as a subtype of classical polyplex, termed “micelle-embedded polyplexes” (mPolyplexes). The impact of different nebulizers on the physicochemical performance of these nanoparticles was investigated, and it was found that various mPolyplexes can be nebulized using vibrating-mesh nebulizers without the loss of gene silencing activity nor a change in physicochemical properties, setting them apart from other nanoparticles such as marketed LNPs. Finally, their therapeutic application was tested ex vivo in human precision-cut lung slices from patients with lung fibrosis. mPolyplexes mediated 52% gene silencing of matrix metalloprotease 7 (MMP7) and a downstream effect on collagen I (Col I) with 33% downregulation as determined via qPCR.
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Research context

PolymersNanomaterials

OpenAlex topics: Inhalation and Respiratory Drug Delivery · RNA Interference and Gene Delivery · Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pharmacy, Ludwig-Maximilians-Universität Munich, Butenandtstrasse 5-13, Haus B, 81377 Munich, Germany

Center for Infections and Genomics of the Lung (CIGL) Justus Liebig University Giessen German Center for Lung Research, Aulweg 132, 35392 Gießen, Germany

Institute of Lung Health (ILH), Justus Liebig University Giessen, Aulweg 128, 35392 Gießen, Germany

Comprehensive Pneumology Center with the CPC-M bioArchive and Institute of Lung Health and Immunity, Helmholtz-Zentrum München, Member of the German Center of Lung Research (DZL), Max-Lebsche-Platz 31, 81377 Munich, Germany

Department of Biochemistry, Gene Center, Ludwig-Maximilians-Universität Munich, Feodor-Lynen-Str. 25, 81377 Munich, Germany

Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Research Network, Member of the German Center for Lung Research (DZL), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hanover, Germany

Center for NanoScience (CeNS), Ludwig-Maximilians-Universität Munich, Schellingstraße 4, 80799 Munich, Germany

Ludwig-Maximilians-Universität Munich, Member of the German Center for Lung Research (DZL), Butenandtstrasse 5-13, Haus B, 81377 Munich, Germany

Funding

H2020 European Research Council · Volkswagen Foundation

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