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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Strategies that Target Tight Junctions for Enhanced Drug Delivery

Author(s): Lorenza González-Mariscal, Yanahi Posadas, Jael Miranda, Perla Yaceli Uc, José Mario Ortega-Olvera and Sandra Hernández

Volume 22, Issue 35, 2016

Page: [5313 - 5346] Pages: 34

DOI: 10.2174/1381612822666160720163656

Price: $65


Ions and molecules move across epithelial barriers by two pathways, the transcellular and the paracellular. The former is taken by lipophilic compounds, or by ions and molecules that move across the plasma membrane through pumps, carriers or exchangers. The second route is regulated by the tight junction (TJ) that through paracellular channels, allows the transport of ions across epithelial barriers. Since, a wide variety of bioactive molecules like peptides, proteins and oligonucleotides cannot use the transcellular route, due to their hydrophilic nature, interest has arisen in devising procedures to open the TJ in a reversible manner for paracellular drug delivery. Here, we describe how different strategies have been devised to enhance the paracellular intestinal absorption of drugs; to open the blood-brain barrier (BBB) to allow the penetration of drugs for the treatment of disorders and tumors of the central nervous system; or to deliver antigens into the subjacent mucosa associated lymphoid tissues, for the development of mucosal vaccines. The strategies described, include the use of peptides, antibodies and miRNAs that target proteins of the apical junctional complex, as well as toxins derived from microorganisms that open the TJ by inducing the contraction of the cortical actomyosin ring. Also, we describe how paracellular absorption, is enhanced by drugs that extract cholesterol from the plasma membrane, surfactants, fatty acids, oligosaccharides, cationic polymers, nitric oxide donors and calcium chelators. Likewise, we explain how the BBB has been opened by employing tumor necrosis factor-α, bradykinin, short chain alkylglycerols, hyperosmotic mannitol and focused ultrasound.

Keywords: Paracellular drug delivery, tight junctions, adherent junctions, blood-brain barrier, blood-tumor barrier, absorption enhancers.

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