Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery
Open accessAbstract
Polymer-based microparticles are in clinical use mainly for their ability to provide controlled release of peptides and compounds, but they are also being explored for their potential to deliver vaccines and drugs as suspensions directly into mucosal sites. It is generally assumed that uptake is mediated by epithelial M cells, but this is often not directly measured. To study the potential for optimizing M cell uptake of polymer microparticles in vivo, we produced sub-micron size PLGA particles incorporating a recombinant protein. This recombinant protein was produced with or without a c-terminal peptide previously shown to have high affinity binding to Claudin 4, a protein associated with M cell endocytosis. While the PLGA nanoparticles incorporate the protein throughout the matrix, much of the protein was also displayed on the surface, allowing us to take advantage of the binding activity of the targeting peptide. Accordingly, we found that instillation of these nanoparticles into the nasal passages or stomach of mice was found to significantly enhance their uptake by upper airway and intestinal M cells. Our results suggest that a reasonably simple nanoparticle manufacture method can provide insight into developing an effective needle-free delivery system.
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Coating CPE30 to PLGA NPs increased uptake by upper airways after intranasal administration and by intestinal M cells after ingestion.
“CPE30, the C-terminal 30 amino acid part of CPE, was coated to PLGA NPs, which increased the uptake by upper airways when administered intranasally or by intestinal M cells after ingestion [101].”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [101]
Claudin 4 functions as a receptor for CPE.
“The latter functions as a receptor for Clostridium perfringens enterotoxin (CPE) and has been recent focus for targeting approaches [101].”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [101]
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- Authors
- Rajapaksa, T. E., Stover-Hamer, M., Fernandez, X., Eckelhoefer, H. A., & Lo, D. D.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Lo, David D.
- ORCID
- Lo, David D.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 142
- Issue
- 2
- Pages
- 196-205
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC2823968
- OpenAlex
- W1973426656
- Cited by
- 137
- References
- 50
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 11 · 2022: 6 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 12 · 2013: 11 · 2012: 14
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health
- Harvard University
- National Institute of Allergy and Infectious Diseases (AI73689, R01AI063426, R43AI058434, R21AI073689)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- claudin-4, M cells, PLGA nanoparticles, targeted drug delivery, mucosal drug delivery, nasal instillation, upper airway, vaccine delivery
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Biological Transport, Cell Line, Cricetulus, Drug Carriers, Cricetinae, Hemagglutinins, Membrane Proteins, Mucous Membrane, Influenza A virus, Peyer's Patches, Polyglycolic Acid, Recombinant Proteins, CHO Cells, Lactic Acid, Mice, Nanoparticles, Claudin-4
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