Abstract
The development of oral insulin using the eligen(®) technology represents a significant advance in insulin administration which is expected to improve the quality of life of diabetic patients. As clinical studies progress, a great deal of interest has focused on the process by which this technology enables insulin absorption from the intestinal lumen into the bloodstream. The eligen(®) technology employs low molecular weight compounds (termed drug delivery agents or carriers) which interact weakly and non-covalently with insulin, increasing its lipophilicity and thereby its ability to cross the gastrointestinal epithelium. In this study we investigated the mechanism of insulin absorption across caco-2 cell monolayers with one of these drug delivery agents, N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases insulin permeability approximately ten fold across cell monolayers and does so without affecting mannitol permeability or disrupting cell membranes. Confocal microscopy and immunocytochemistry revealed that insulin is transported transcellularly without detectable alteration of the tight junctions between adjacent cells. SNAC also appears to play some role in protecting insulin from proteolytic degradation, potentially allowing for more intact insulin to be available at the site of absorption.
Keywords: oral insulin, caco-2 cells, transcellular absorption, occludin, circular dichroism
Current Drug Delivery
Title: Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies
Volume: 2 Issue: 2
Author(s): Dmitry Malkov, Robert Angelo, Huai-zhen Wang, Elizabeth Flanders, Heather Tang and Isabel Gomez-Orellana
Affiliation:
Keywords: oral insulin, caco-2 cells, transcellular absorption, occludin, circular dichroism
Abstract: The development of oral insulin using the eligen(®) technology represents a significant advance in insulin administration which is expected to improve the quality of life of diabetic patients. As clinical studies progress, a great deal of interest has focused on the process by which this technology enables insulin absorption from the intestinal lumen into the bloodstream. The eligen(®) technology employs low molecular weight compounds (termed drug delivery agents or carriers) which interact weakly and non-covalently with insulin, increasing its lipophilicity and thereby its ability to cross the gastrointestinal epithelium. In this study we investigated the mechanism of insulin absorption across caco-2 cell monolayers with one of these drug delivery agents, N-[8-(2-hydroxybenzoyl)amino] caprylate (SNAC). Our results show that SNAC increases insulin permeability approximately ten fold across cell monolayers and does so without affecting mannitol permeability or disrupting cell membranes. Confocal microscopy and immunocytochemistry revealed that insulin is transported transcellularly without detectable alteration of the tight junctions between adjacent cells. SNAC also appears to play some role in protecting insulin from proteolytic degradation, potentially allowing for more intact insulin to be available at the site of absorption.
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Cite this article as:
Malkov Dmitry, Angelo Robert, Wang Huai-zhen, Flanders Elizabeth, Tang Heather and Gomez-Orellana Isabel, Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies, Current Drug Delivery 2005; 2 (2) . https://dx.doi.org/10.2174/1567201053586001
DOI https://dx.doi.org/10.2174/1567201053586001 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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