2. Academic Validation
  3. Gastrointestinal Device-Mediated Delivery of mRNA-Lipid Nanoparticles Achieves Distinct Expression and Biodistribution in Mice and Pigs

Gastrointestinal Device-Mediated Delivery of mRNA-Lipid Nanoparticles Achieves Distinct Expression and Biodistribution in Mice and Pigs

  • ACS Appl Mater Interfaces. 2024 Dec 11;16(49):67192-67202. doi: 10.1021/acsami.4c11819.
David Schultz 1,  Paul J Kempen 1 2,  Susanne Primdahl 1,  Maria Pereverzina 3,  Anders H Uhrenfeldt 4,  Enrique M D Alba 5,  Jan Andreasen 5,  Henrik D Pedersen 4,  Cody Cleveland 5,  Todd Duncombe 3,  Jonas Ahnfelt-Ro Nne 4,  Rikke K Kirk 4,  Isabelle B Pfander 3,  Drago Sticker 3,  Jorrit J Water 3,  Stephen T Buckley 3,  Thomas L Andresen 1,  Andrew J Urquhart 1
Affiliations

Affiliations

  • 1 Department of Health Technology, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
  • 2 National Centre for Nano Fabrication and Characterization, Technical University of Denmark, Kongens Lyngby 2800, Denmark.
  • 3 Global Research Technologies, Novo Nordisk A/S, Målo̷v 2760, Denmark.
  • 4 Global Drug Discovery, Novo Nordisk A/S, Målo̷v 2760, Denmark.
  • 5 Device & Delivery Solutions, Novo Nordisk A/S, Hillero̷d 3400, Denmark.
PMID: 39621822 DOI: 10.1021/acsami.4c11819
Abstract

Recent investigations into autonomous ingestible microjet devices have demonstrated the feasibility of delivering many drug modalities directly into the gastrointestinal (GI) wall via the oral route. However, the expression and biodistribution of mRNA after such injections remain unexplored. mRNA-lipid nanoparticles (mRNA-LNPs) are promising therapeutics for treating or vaccinating against many diseases and pathogens. Today, mRNA-LNPs are given as injections, necessitating trained medical personnel and resulting in reduced patient compliance. Here, we elucidate the expression and biodistribution of mRNA-LNPs after injection into the gastric and intestinal walls of mice and minipigs. We see a controlled release of mRNA from the stomach and intestine with mRNA in both plasma and lymph nodes, leading to a broad biodistribution profile, which could lead to better immunization after vaccination. Our results substantiate the argument that ingestible microjet devices facilitate a viable route of administration for use as an alternative to injections of mRNA-LNP.

Keywords

administration route; biodistribution; device-mediated drug delivery; gastrointestinal drug delivery; lipid nanoparticles; mRNA.

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