Regular Article
Modulation of Intestinal Permeability: An Innovative Method of Oral Drug Delivery for the Treatment of Inherited and Acquired Human Diseases

https://doi.org/10.1006/mgme.1998.2667Get rights and content

Abstract

Conventional forms of administrations of nonabsorbable drugs and peptides rely on their parenteral injection. The intestinal epithelium represents the major barrier to the oral absorption of these therapeutical agents into the systemic circulation. Recently, a number of innovative drug delivery approaches have been developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. Zonula occludens toxin, a recently discovered protein elaborated byVibrio cholerae,provided tools for gaining more insights on the pathophysiology of the regulation of intestinal permeability and to developing alternative approaches for the oral delivery of drugs and macromolecules normally not absorbed through the intestine.

References (32)

  • M Cereijido

    Evolution of ideas on the tight junction

    Tight Junctions

    (1992)
  • EE Schneeberger et al.

    Development of intercellular junctions in the pulmonary epithelium of the foetal lamb

    J Cell Sci

    (1978)
  • JL Madara et al.

    Structural basis for physiological regulations of paracellular pathways in intestinal epithelia

    J Membr Biol

    (1987)
  • MR Mazariegos et al.

    Alteration of tight junctional permeability in the rat parotid gland after isoproteranol stimulation

    J Cell Biol

    (1984)
  • C Sardet et al.

    The surface epithelium of teleostean fish gills. Cellular and junctional adaptations of the chloride cell in relation to salt adaptation

    J Cell Biol

    (1979)
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    Supported by the National Institute of Health Grants DK-48373 and AI-35740.

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