Exploring Mechanisms of Lipid Nanoparticle‐Mucus Interactions in Healthy and Cystic Fibrosis Conditions

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Abstract: Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR‐based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerge as versatile non‐viral gene delivery systems that can help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein‐loaded LNP‐mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics (BD) simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Exploring Mechanisms of Lipid Nanoparticle‐Mucus Interactions in Healthy and Cystic Fibrosis Conditions ; day:13 ; month:04 ; year:2024 ; extent:13
Advanced healthcare materials ; (13.04.2024) (gesamt 13)

Creator: Tafech, Belal
Rokhforouz, Mohammad‐Reza
Leung, Jerry
Sung, Molly MH
Lin, Paulo JC
Sin, Don D.
Lauster, Daniel
Block, Stephan
Quon, Bradley S.
Tam, Ying
Cullis, Pieter
Feng, James J.
Hedtrich, Sarah

DOI: 10.1002/adhm.202304525

URN: urn:nbn:de:101:1-2024041414050719858123

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:51 AM CEST

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Tafech, Belal
Rokhforouz, Mohammad‐Reza
Leung, Jerry
Sung, Molly MH
Lin, Paulo JC
Sin, Don D.
Lauster, Daniel
Block, Stephan
Quon, Bradley S.
Tam, Ying
Cullis, Pieter
Feng, James J.
Hedtrich, Sarah

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Exploring Mechanisms of Lipid Nanoparticle‐Mucus Interactions in Healthy and Cystic Fibrosis Conditions

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Other Objects (12)

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