| Transport of nanocarriers across gastrointestinal epithelial cells by a new transcellular route induced by targeting ICAM-1. | |
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MedLine Citation:
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PMID: 22698938 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bioavailability of oral drugs, particularly large hydrophilic agents, is often limited by poor adhesion and transport across gastrointestinal (GI) epithelial cells. Drug delivery systems, such as sub-micrometer polymer carriers (nanocarriers, NCs) coupled to affinity moieties that target GI surface markers involved in transport, may improve this aspect. To explore this strategy, we coated 100-nm polymer particles with an antibody to ICAM-1 (a protein expressed on the GI epithelium and other tissues) and evaluated targeting, uptake, and transport in human GI epithelial cells. Fluorescence and electron microscopy, and radioisotope tracing revealed that anti-ICAM NCs specifically bound to cells in culture, were internalized via CAM-mediated endocytosis, trafficked by transcytosis across cell monolayers without disrupting the permeability barrier or cell viability, and enabled transepithelial transport of a model therapeutic enzyme (α-galactosidase, deficient in lysosomal Fabry disease). These results indicate that ICAM-1 targeting may provide delivery of therapeutics, such as enzymes, to and across the GI epithelium. |
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Authors:
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Rasa Ghaffarian; Tridib Bhowmick; Silvia Muro |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-06-12 |
Journal Detail:
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Title: Journal of controlled release : official journal of the Controlled Release Society Volume: 163 ISSN: 1873-4995 ISO Abbreviation: J Control Release Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-01 Completed Date: 2013-02-26 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: Netherlands |
Other Details:
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Languages: eng Pagination: 25-33 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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Fischell Department of Bioengineering, 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport Caco-2 Cells Drug Carriers / administration & dosage* Gastrointestinal Tract / cytology Humans Immunoglobulin G / administration & dosage* Intercellular Adhesion Molecule-1 / immunology, metabolism* Nanostructures / administration & dosage* Polystyrenes / administration & dosage Tumor Necrosis Factor-alpha / pharmacology alpha-Galactosidase / administration & dosage* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL098416/HL/NHLBI NIH HHS; R01-HL98416/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Drug Carriers; 0/ICAM1 protein, human; 0/Immunoglobulin G; 0/Polystyrenes; 0/Tumor Necrosis Factor-alpha; 126547-89-5/Intercellular Adhesion Molecule-1; EC 3.2.1.22/alpha-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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