Editors' ChoiceDiabetes

“Red Rover, Red Rover, Send Insulin Right Over!”

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Science Translational Medicine  22 Feb 2012:
Vol. 4, Issue 122, pp. 122ec32
DOI: 10.1126/scitranslmed.3003872

In the game of “Red Rover,” children charge at a wall of linked hands, attempting to break down the barrier and emerge triumphant on the other side. Similarly, Su et al. have devised a clever nanoparticle-based method to send insulin through a chain of intestinal epithelial cells—an approach that would allow oral administration of insulin formulations, thus forgoing injections and improving patient convenience and compliance.

Proteases and adhesion proteins that maintain tight cell–cell junctions prevent the passage of intact insulin across the intestinal wall (the epithelium). However, these enzymes and proteins cannot function without certain metal ions, such as Ca2+ and Zn2+. Taking advantage of this phenomenon, Su et al. designed insulin-loaded nanoparticles (NPs) for oral delivery that contained diethylene triamine pentaacetic acid (DTPA), a metal cation chelator. The authors found that DTPA reduced the number of free Ca2+ along the intestinal wall. In this way, proteases were less likely to degrade insulin, and adhesion proteins were disrupted, which opened up tight junctions between cells and allowed insulin to pass from the intestinal lumen to the bloodstream.

In rat intestinal segments, the percentage of intact (nondegraded) insulin was fivefold higher when insulin was formulated with DTPA (versus no DTPA). When the insulin–NPs were administered orally to diabetic rats, radiolabeled insulin was detected in the kidney and bladder, providing proof of successful systemic absorption. Although no detectable plasma concentrations of insulin were observed after an oral dose of free insulin, ingestion of insulin–NPs resulted in 20% of the insulin reaching the bloodstream. The peak plasma concentration occurred after 4 hours, and a prolonged reduction in blood glucose levels was achieved. The strategy used by Su et al. is an exciting approach in the development of an oral insulin formulation and promises to break down barriers in the search for more effective ways to manage diabetes.

F.-Y. Su et al., Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials 33, 2801–2811 (2012). [Abstract]

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