Bringing Sugar to the Core: A Core-Shell Solution to Insulin Replacement

by | Sep 21, 2018

Lipid bilayer-coated polymeric nanoparticles can at as a long-acting, glucose-responsive insulin delivery system in type-I diabetes.
Sugar Sweet

Sugar can be seen as a double-edged sword: it tastes great, and it can provide a high amount of energy to the body for almost direct use, but it can also be very bad for your health, especially, if the body’s mechanism for sugar uptake is malfunctioning.

A severe cause of this is diabetes mellitus type I–an autoimmune disease that deprives the body of the ability to produce insulin. Insulin, however, is required as a signal to take up glucose into cells for further processing and would normally be produced by the body, if the blood sugar exceeds a certain level.

Until now diabetes type I, cannot be cured or outright prevented and the only therapy is the self-injection of insulin when the blood sugar level demands it. This tedious process requires the patient to constantly monitor his blood glucose (BG) level and inject insulin subcutaneously before meals, usually at least three times per day.

How important it is to control the BG level, becomes immediately clear when one assess potential consequences: Continuous high glucose levels result in a systemic metabolic disorder that leads to nephropathies, cardiovascular disease, nerve damage, and blindness. On the other hand, too frequent insulin injections can result in hypoglycemia with severe complications.

A way of insulin delivery that requires less self-monitoring, less patient-compliance, and less uncomfortable injections is therefore highly desired for diabetes type I patients. Insulin delivery routes studied to date include transdermal injection, oral administration (hampered by enzymatic degradation of insulin), nasal or pulmonary administration (requiring delivery devices and yet failing in delivering precise dosages), and subcutaneous implantation.

A popular recent approach is the injection of a high-dosed insulin mixture that contains fast and slow acting analogues. However, applying such a high dose represents a potential hazard to the patient. In-situ gel preparations and subcutaneous implantation results in slow and even insulin release but this release does not respond to a changing BG level of the patient. In consequence, intelligent insulin delivery systems employ glucose-sensing moieties. The classical moieties comprise phenylboronic acid (PBA) derivatives, glucose-binding proteins like concanavalin A, and glucose oxidase. Although these systems offer self-regulating insulin release in response to BG levels, they are still short-term solutions that require repeated injections.

Qing Lin, Ling Zhang, and their co-workers from Sichuan University, P.R. China, report a novel, long-acting, glucose-responsive insulin delivery system based on a lipid bilayer-coated polymeric nanoparticle.

Dextran nanoparticles functionalized with ethoxy acetal (ace-DEX NPs) are loaded with insulin, glucose oxidase (GOx), and catalase (CAT) to form a glucose-sensitive inner core. This design succeeds in preventing the leakage of insulin into the blood in hypoglycemic conditions and in modulating insulin release in accordance to BG level. Long circulation abilities are assured by an outer shell derived from red blood cell membranes (RBCm). This shell comes equipped with GLUT proteins that let glucose pass so that is can be oxidized by GOx from the core.

The gluconic acid generated by glucose oxidation degrades the dextran of the cargo particles, thereby releasing the insulin. In consequence, the system is controlled both automatically and continuously by the blood glucose level – secretion is stopped at normoglycemia but triggered by hyperglycemia.

Initial studies on type-I diabetic mice achieved stable normoglycemia for 24 h and a slow trend toward hyperglycemia within four days. Future research aims to harness the month-long circulation ability of RBCs toward a month-lasting BG-responsive insulin delivery system.
The involved scientist Yu Fu believes that the system has “potential to overcome the drawbacks of conventional insulin administration. Collectively, with great practical value, the current study lays a solid foundation to develop further intravenous glucose-responsive insulin delivery.”


Find this and other exciting research on the Advanced Functional Materials homepage.

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