Editors' ChoiceDiabetes

Sugar Coat It

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Science Translational Medicine  29 May 2013:
Vol. 5, Issue 187, pp. 187ec88
DOI: 10.1126/scitranslmed.3006578

A finger prick of blood is all it takes to measure blood glucose levels; the diabetic patient can then respond by injecting insulin, if necessary. Delivering insulin on time, however, is challenging because so many daily events affect glucose levels, including diet, exercise, endogenous insulin production, site of insulin delivery, and metabolic state. To take the patient’s mind off constant glucose surveillance and insulin delivery, Gu et al. now report on sugar-coated nanoparticles that can not only sense glucose but also secrete the appropriate amount of insulin to maintain normal sugar levels in the body.

Material-based versions of the “artificial pancreas” already exist that can automatically detect glucose levels and secrete insulin on demand. However, they often lack the mechanical strength, are eliminated from the body too fast, are slow to respond to glucose changes, or allow insulin to leak out. Gu et al. developed an injectable system that addresses these issues while remaining biocompatible and easy to administer. The authors used coated dextran nanoparticles with chitosan and alginate, imparting alternating positive and negative charges, respectively. Electrostatic interactions kept the gel’s integrity and prevented particle migration after application into the subcutaneous dorsum of mice. Insulin and glucose-specific enzymes were encapsulated in the particles by using conventional emulsion techniques, enabled by chemical modification of dextran with acetal groups. The same acetal groups also made the polymer pH-sensitive. Blood glucose that diffused into the gel was converted by these enzymes to gluconic acid, causing a slight local change in acidity that degraded the gel-like structure and released the encapsulated insulin. A single injection of the glucose-sensing, insulin-loaded gel kept mice with type 1 diabetes at normal blood-sugar levels for 10 days.

This glucose-responsive particle is an exciting approach for controlling diabetes, but the particle has a long way to go before reaching the clinic. Other than long-term safety, dosing, and efficacy studies, the authors would need to show that the particle responds quickly and effectively to changes in glucose levels in many different scenarios, including after large meals and strenuous exercise. Nevertheless, this nanoformulation from Gu et al. provides rays of hope for diabetic patients, with the potential for self-regulated diabetes management.

Z. Gu et al., Injectable nano-network for glucose-mediated insulin delivery. ACS Nano., 2 May 2013 (10.1021/nn400630x). [Abstract]

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