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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Tight junction modulation and its relationship to drug delivery
Noha N Salama1, Natalie D Eddington, Alessio Fasano
1Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, 100 Penn Street, Baltimore, Maryland 21201, USA.
Advanced Drug Delivery Reviews
|March 7, 2006
Summary
Zonula Occludens toxin (Zot) enhances drug delivery by temporarily opening tight junctions (TJs) in the intestinal epithelium. This facilitates the paracellular transport of hydrophilic drugs, improving bioavailability and enabling novel therapeutic strategies.
Area of Science:
- Pharmacology
- Cell Biology
- Drug Delivery
Background:
- Therapeutic agents must cross biological membranes to reach their site of action.
- Drug transport occurs via transcellular or paracellular pathways, with the latter crucial for hydrophilic molecules.
- The paracellular pathway is regulated by tight junctions (TJs), whose complex structure and function were poorly understood, hindering drug delivery advancements.
Purpose of the Study:
- To investigate the potential of Zonula Occludens toxin (Zot) as an absorption enhancer for paracellular drug transport.
- To evaluate the efficacy of Zot and its fragment DeltaG in improving the delivery of low bioavailability drugs.
Main Methods:
- Review of in vivo and in vitro studies on Zot's effect on intestinal epithelium.
- Analysis of Zot's mechanism involving the modulation of tight junctions (TJs).
Main Results:
- Zot and its biologically active fragment DeltaG effectively increase the transport of paracellular markers and poorly absorbed drugs.
- Zot induces transient opening of TJs, suggesting a safe mechanism for enhanced drug absorption.
Conclusions:
- Zot represents a novel approach for improving drug delivery by enhancing paracellular transport.
- The transient nature of TJ opening by Zot offers a promising strategy for safe and effective delivery of therapeutic agents.
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