Cited by 137Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

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Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery

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Rajapaksa, Thejani E., Stover-Hamer, Mary, Fernandez, Xiomara, Eckelhoefer, Holly A., Lo, David D.·2010·Journal of Controlled Release

DOI 10.1016/j.jconrel.2009.10.033PMC PMC2823968

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Abstract

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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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)
DOI: 10.1016/j.jconrel.2009.10.033
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery

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