In his lab on N.C. State University’s Centennial Campus, Dr. Zhen Gu is battling an enormous global health threat with the tiniest of particles.

Gu is using nanotechnology to mimic the cells that maintain blood-sugar levels in a healthy person’s body – without taking multiple shots a day, as many diabetics currently must do.

“Micro-sponges” expand to release insulin in response to elevated blood glucose.

“We’ve created a ‘smart’ system that is injected into the body and responds to changes in blood sugar by releasing insulin, effectively controlling blood-sugar levels,” Gu said.[1]

“We’ve tested the technology in mice, and one injection was able to maintain blood sugar levels in the normal range for up to 10 days.  Even one month is also expected.”[2]

A patient with diabetes doesn’t produce enough insulin, the hormone that transfers glucose from the bloodstream to the body’s cells.  The extended bouts of elevated blood sugar that result can lead to heart disease, kidney failure, blindness and limb amputations, among other health problems.

Dr. Zhen Gu

Gu, 34, notes that his own grandmother died of complications from the disease. There are already 382 million diabetics worldwide, and the U.S. Centers for Disease Control and Prevention predicts that if current trends continue, one in three adults in the United States will have diabetes by 2050.

A Type 1 diabetic who is diagnosed at age 10 and lives to age 80 typically takes four shots of insulin a day – or 102,200 injections over the course of a lifetime – along with a similar number of finger pricks to check his or her blood sugar.  The injections can be painful – especially for children – and administering too much or too little insulin can be life-threatening.

But Gu, an assistant professor in the joint biomedical engineering program shared by NC State and UNC-Chapel Hill, is investigating several methods to mimic the cells in the pancreas that dispense minute, appropriate doses of insulin in real time:

• Injectable nanoparticles with a solid core of insulin combined with special enzymes.  When the enzymes are exposed to glucose, they turn the glucose into an acid that breaks down the structure and releases the insulin.  In mice, Gu said, one injection can now maintain normal blood sugar levels for as long as 16 days.
• “Micro-sponges” made of chitosan, a material found in shrimp and crab shells, surrounding an inner reservoir of insulin.  As a patient’s blood sugar rises, it triggers a reaction that charges the strands of chitosan so that they push away from one another, creating gaps that allow the insulin to escape into the bloodstream.  Then, as the insulin reduces blood glucose, the chitosan strands lose their charge and come back together, trapping the insulin that remains in the sponge.  At 250 micrometers – about four times the width of a human hair – the sponges are injectable.
• An ultrasound device that a patient could use to painlessly release implanted insulin into the bloodstream.
• Synthetic “vesicles” that would deliver insulin to cells as blood sugar rises – as well as glucagon, a hormone that raises blood sugar, if glucose levels fall too low.[3]

Dr. John Buse, director of the Diabetes Care Center at the UNC School of Medicine and a former president of the American Diabetes Association, is a collaborator on Gu’s research.

When he first heard Gu talk about his ideas for nano-delivery of insulin, “My jaw just dropped,” Buse said.  “The work that Zhen is doing is incredibly cutting edge.”

The dual-vesicle system that would deliver insulin or glucagon as needed is particularly noteworthy.

“Effectively, it would be closer to a cure than anything we envision now,” Buse said. “It’s really extremely exciting.  And the only thing that limits how fast this moves is money.”

Buse notes that diabetes has almost doubled in prevalence in the United States just since 1994, and Americans now spend $245 billion a year treating the disease.[4]

The research is in keeping with the University system’s strategic plan, which calls for strategic investments to “help address North Carolina’s health care needs by rethinking outdated models of care, conducting life-saving research, and training the next generation of medical professionals.”[5]

Gu’s research has ramifications well beyond the state’s borders, though, and he is eager to move to testing in pigs, then humans.  He likes to share an e-mail he received last year from a diabetic who heard about his work and immediately volunteered for clinical trials.

How long will that take?

“I’m very confident about our formulations,” he said.  “Could it be one year?  Could it be three years?  Could it be 10 years?  It depends on money,” he said.[6]

[1] http://news.ncsu.edu/2013/05/gu-insulin-2013/

[2] http://news.engr.ncsu.edu/2014/02/new-research-could-eliminate-insulin-injections-for-diabetics/

[3] American Diabetes Association presentation, NC State University, Oct. 7, 2014.

[4] Ibid.

[5] http://www.northcarolina.edu/sites/default/files/strategic_directions_2013-2018_0.pdf, p. 55.

[6] American Diabetes Association presentation, NC State University, Oct. 7, 2014.