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Tight junction modulation and its relationship to drug delivery. | LitMetric

Tight junction modulation and its relationship to drug delivery.

Adv Drug Deliv Rev

Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, 100 Penn Street, Baltimore, Maryland 21201, USA.

Published: April 2006

AI Article Synopsis

  • Drugs must cross biological membranes to be effective, typically through transcellular or paracellular pathways, with hydrophilic drugs often using the latter route.
  • Tight junctions (TJs) play a critical role in paracellular transport, but a thorough understanding of their structure and function has been lacking, hindering drug delivery improvements.
  • Recent developments, such as Zonula Occludens toxin (Zot), show promise for enhancing drug absorption by temporarily opening TJs, potentially offering a new method for safe therapeutic delivery.

Article Abstract

In order for therapeutic agents to exert their pharmacological effects, they have to cross the biological membranes into the systemic circulation and reach the site of action. Drugs cross the membranes by one of two pathways; paracellular or transcellular. Most drugs are transported transcellularly depending on their physiocochemical properties, however the paracellular route is usually the main route of absorption for hydrophilic drugs (proteins, peptides, etc.). The paracellular pathway is governed by the tight junctions (TJs). The modulation of the TJs by absorption enhancers for paracellular drug transport enhancement and hence drug delivery improvement has been hampered for so many years by lack of comprehensive understanding of the structure and function of the TJs. The TJs are a multiple unit structure composed of multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ proteins identified include transmembrane proteins; occludin and claudin, and cytoplasmic plaque proteins; ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Among the new absorption enhancers that evolved in the past few years is Zonula Occludens toxin, Zot. In vivo and in vitro studies have shown that Zot and its biologically active fragment DeltaG could be effectively used to increase the transport/absorption of paracellular markers and low bioavailable drugs across the intestinal epithelium. Above all, the transient opening of the TJs by Zot suggests that it could be used as a novel approach for the safe drug delivery of therapeutic agents.

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Source
http://dx.doi.org/10.1016/j.addr.2006.01.003DOI Listing

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