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Transmembrane transport of peptide type compounds: prospects for oral deliverySynthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.
Document ID
Document Type
Reprint (Version printed in journal)
Lipka, E.
(Inc. Ann Arbor, MI 48108, United States)
Crison, J.
Amidon, G. L.
Date Acquired
August 21, 2013
Publication Date
May 1, 1996
Publication Information
Publication: Journal of controlled release : official journal of the Controlled Release Society
Volume: 39
Issue: 2-3
ISSN: 0168-3659
Subject Category
Life Sciences (General)
Distribution Limits
NASA Discipline Regulatory Physiology
Non-NASA Center
Review, Tutorial
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