Transport of nanocarriers across gastrointestinal epithelial cells by a new transcellular route induced by targeting ICAM-1.
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.
Fischell Department of Bioengineering, 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA.
Rasa
R
Ghaffarian
Tridib
T
Bhowmick
Silvia
S
Muro
D001692:Biological Transport; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000008:administration & dosage*; D041981:Gastrointestinal Tract / Q000166:cytology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D049329:Nanostructures / Q000008:administration & dosage*; D011137:Polystyrenes / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000519:alpha-Galactosidase / Q000008:administration & dosage*
D004337:Drug Carriers; C573420:ICAM1 protein, human; D007074:Immunoglobulin G; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000519:alpha-Galactosidase