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

[摘要] 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 (alpha-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. (C) 2012 Elsevier B.V. All rights reserved.

[发布日期] 2012-10-10

[效力级别]  Proceedings Paper

[关键词] ICAM-1;Polymer nanocarriers;Gastrointestinal epithelium;Trancytosis transport;Enzyme delivery