Editors' ChoiceDiabetes

Insulin delivery never tasted so good

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Science Translational Medicine  20 Jul 2016:
Vol. 8, Issue 348, pp. 348ec117
DOI: 10.1126/scitranslmed.aah3550

With approximately 8.3% of the adult population suffering from diabetes, there is a high likelihood that each of us knows someone with the disease. Regardless of whether they suffer from a dysfunctional pancreas (Type I diabetes) or insulin resistance (Type II diabetes), nearly all diabetic patients must pharmacologically manage the disease. Effective insulin injections require careful blood sugar monitoring and painful needle sticks daily. Wearable drug infusion pumps provide considerable advantages over daily insulin injections but are expensive, must be worn at all times, and can fail with catastrophic consequences. An ideal solution would be oral insulin delivery but this approach does not yet appear feasible. In a new study in rats, Lee et al. provide evidence that dual-functionalized nanocarriers can deliver insulin to the bloodstream for prolonged periods of time in a controlled way.

Prior attempts to engineer oral delivery devices have been suboptimal because they have focused on sheltering encapsulated payloads from the highly acidic stomach environment. Although this is an important consideration, surviving the stomach is only half the battle, as the controlled delivery system still needs to be capable of trafficking across tight junctions between intestinal epithelial cells to reach the bloodstream. Lee et al. used self-assembled pluronic nanocarriers to entrap insulin. These nanocarriers were then dual-functionalized by coating with the biopolymer chitosan for particle acid protection and to increase intestinal residence time, as well as the peptide zonula occludens toxin (ZOT) to facilitate the ability of the nanocarriers to cross the gut epithelial barrier. The dual-functionalized nanocarriers showed improved transport across single epithelial monolayers in vitro compared with nanoparticles carrying peptide alone or nanocarriers functionalized with just chitosan or ZOT peptide. The authors were able to recapitulate these findings in vivo. Treatment of diabetic rats with orally delivered dual-functionalized nanocarriers resulted in a decrease in serum blood glucose concentrations for up to 24 hours. In contrast, none of the control groups receiving orally-delivered nanocarriers that were not dual-functionalized resulted in decreased serum glucose concentrations. Meanwhile, the beneficial effects of subcutaneously-delivered insulin on serum glucose in this rat model only lasted 6 to 8 hours.

Although more studies are needed to demonstrate how effective dual-functionalized nanocarriers will be for managing blood sugar peaks and valleys long-term, the Lee et al. study hints at the future potential of this engineered system for providing a daily pill to manage diabetes.

J. H. Lee et al., ZOT-derived peptide and chitosan functionalized nanocarrier for oral delivery of protein drug. Biomaterials 103, 160–169. (2016). [Abstract]

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