Articles by Rasa Ghaffarian in JoVE
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers Rasa Ghaffarian1, Silvia Muro1,2 1Fischell Department of Bioengineering, University of Maryland, 2Institute for Bioscience and Biotechnology Research, University of Maryland Many therapeutic applications require safe and efficient transport of drug carriers and their cargoes across cellular barriers in the body. This article describes an adaptation of established methods to evaluate the rate and mechanism of transport of drug nanocarriers (NCs) across cellular barriers, such as the gastrointestinal (GI) epithelium.
Other articles by Rasa Ghaffarian on PubMed
Transport of Nanocarriers Across Gastrointestinal Epithelial Cells by a New Transcellular Route Induced by Targeting ICAM-1 Journal of Controlled Release : Official Journal of the Controlled Release Society. Oct, 2012 | Pubmed ID: 22698938 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.