Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 171, Issue -, Pages 266-288Publisher
ELSEVIER
DOI: 10.1016/j.addr.2021.02.008
Keywords
Epithelial permeability; Tight junctions; Paracellular pathway; Claudin; Occludin; Zonula occludens
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Research focuses on modulating intercellular tight junctions to enhance drug absorption and bioavailability, with challenges in commercialization. Target-specific permeation enhancers have potential clinical applications.
Intercellular tight junctions represent a formidable barrier against paracellular drug absorption at epithe-lia (e.g., nasal, intestinal) and the endothelium (e.g., blood-brain barrier). In order to enhance paracellular transport of drugs and increase their bioavailability and organ deposition, active excipients modulating tight junctions have been applied. First-generation of permeation enhancers (PEs) acted by unspecific interactions, while recently developed PEs address specific physiological mechanisms. Such target speci-fic tight junction modulators (TJMs) have the advantage of a defined specific mechanism of action. To date, merely a few of these novel active excipients has entered into clinical trials, as their lack in safety and efficiency in vivo often impedes their commercialisation. A stronger focus on the development of such active excipients would result in an economic and therapeutic improvement of current and future drugs. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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