Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies

Authors: Malkov, Dmitry; Angelo, Robert; Wang, Huai-zhen; Flanders, Elizabeth; Tang, Heather; Gomez-Orellana, Isabel

Source: Current Drug Delivery, Volume 2, Number 2, April 2005 , pp. 191-197(7)

Publisher: Bentham Science Publishers

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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

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567201053586001

Affiliations: 1: Emisphere Technologies, Inc., 765 Old Saw Mill River Road, Tarrytown, NY 10591, USA.

Publication date: 2005-04-01

More about this publication?

The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.

The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.

Oral Delivery of Insulin with the eligen(®) Technology: Mechanistic Studies

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