Cited by 158Extracellular vesicles in diseaseInhalation and Respiratory Drug DeliveryNanoparticle-Based Drug Delivery

Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung

Open access
Popowski, Kristen D., López de Juan Abad, Blanca, George, Arianna, Silkstone, Dylan, Belcher, Elizabeth, Chung, Jaewook, Ghodsi, Asma, Lutz, Halle +5 more·2022·Extracellular Vesicle

Abstract

Respiratory diseases are among the leading causes of morbidity and mortality worldwide, coupled with the ongoing coronavirus disease 2019 (COVID-19) pandemic. mRNA lipid nanoparticle (LNP) vaccines have been developed, but their intramuscular delivery limits pulmonary bioavailability. Inhalation of nanoparticle therapeutics offers localized drug delivery that minimizes off targeted adverse effects and has greater patient compliance. However, LNP platforms require extensive reformulation for inhaled delivery. Lung-derived extracellular vesicles (Lung-Exo) offer a biological nanoparticle alternative that is naturally optimized for mRNA translation and delivery to pulmonary cells. We compared the biodistribution of Lung-Exo against commercially standard biological extracellular vesicles (HEK-Exo) and LNPs (Lipo), where Lung-Exo exhibited superior mRNA and protein cargo distribution to and retention in the bronchioles and parenchyma following nebulization administration. This suggests that inhaled Lung-Exo can deliver mRNA and protein drugs with enhanced pulmonary bioavailability and therapeutic efficacy.

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Crossref · 10.1016/j.vesic.2022.100002

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  • Popowski et al. developed an inhalable vaccine utilizing lung-derived exosomes for mRNA and protein cargos; Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against SARS-CoV-2.

    “They indicated that Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against severe acute respiratory syndrome coronavirus -2 (SARS-COV-2) [135].”

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Research works printed but not linked: 1

  1. [13]Walsh E.E. Frenck R.W.J. Falsey A.R. Kitchin N. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates N Engl J Med 383 25 2020 2439 2450 10.1056/NEJMoa2027906 33053279 PMC7583697 · DOI · Paper page

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Authors
Popowski, K. D., López de Juan Abad, B., George, A., Silkstone, D., Belcher, E., Chung, J., Ghodsi, A., Lutz, H., Davenport, J., Flanagan, M., Piedrahita, J., Dinh, P.-U. C., & Cheng, K.
Affiliations
  • North Carolina State University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Cheng, Ke
Venue
Extracellular Vesicle
Publisher
Elsevier BV
Published
2022-12
Volume
1
Pages
100002
ISSN
2773-0417 (ISSN-L)
OpenAlex
W4282972187
Cited by
158
References
33
Citations by year
2026: 28 · 2025: 51 · 2024: 50 · 2023: 19 · 2022: 10
FWCI
10.61
Type
journal article
Language
en
Open access
Locations
  • Extracellular Vesicle (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institutes of Health (HL149940, HL137093, HL123920, HL147357, HL146153, HL144002)
  • American Heart Association Inc (18TPA34230092, 19EIA34660286)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
exosomes, pulmonary drug delivery, mRNA delivery, lipid nanoparticle vaccine, nebulization, protein drug delivery, respiratory diseases, COVID-19 vaccines

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