Document Detail


Transport of nanocarriers across gastrointestinal epithelial cells by a new transcellular route induced by targeting ICAM-1.
MedLine Citation:
PMID:  22698938     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rasa Ghaffarian; Tridib Bhowmick; Silvia Muro
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Publication Detail:
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:
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:
Created Date:  2012-10-01     Completed Date:  2013-02-26     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  25-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Fischell Department of Bioengineering, 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
R01 HL098416/HL/NHLBI NIH HHS; R01-HL98416/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
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
Comments/Corrections

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