Transport of nanocarriers across gastrointestinal epithelial cells by a new transcellular route induced by targeting ICAM-1.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleTransport of nanocarriers across gastrointestinal epithelial cells by a new transcellular route induced by targeting ICAM-1.
Publication TypeJournal Article
Year of Publication2012
AuthorsGhaffarian, R, Bhowmick, T, Muro, S
JournalJ Control Release
Volume163
Issue1
Pagination25-33
Date Published2012 Oct 10
ISSN1873-4995
Keywordsalpha-Galactosidase, Biological Transport, Caco-2 Cells, Drug Carriers, Gastrointestinal Tract, Humans, Immunoglobulin G, Intercellular Adhesion Molecule-1, Nanostructures, Polystyrenes, Tumor Necrosis Factor-alpha
Abstract

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.

DOI10.1016/j.jconrel.2012.06.007
Alternate JournalJ Control Release
PubMed ID22698938
PubMed Central IDPMC3462239
Grant ListR01 HL098416 / HL / NHLBI NIH HHS / United States
R01-HL98416 / HL / NHLBI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States