Researchers at N.C. State and UNC-Chapel Hill are working on a new form of blood sugar regulation in diabetic patients based on nanotechnology. 

This new nanotechnology, if it passes testing, will allow patients to release insulin with a small ultrasound device. This technology would eliminate the need for diabetics to administer insulin injections multiple times a day, meaning patients would be able to go days between each injection. 

Zhen Gu, the senior author of a paper on the research and assistant professor in the joint biomedical engineering program at N.C. State and UNC-Chapel Hill, initiated the idea and led the research. 

According to Gu, the ultrasound device involves patients injecting biocompatible and biodegradable nanoparticles into their skin. The nanoparticles are comprised of poly (lactic-co-glycolic) acid, or PLGA, and each particle contains a small amount of insulin.

Yun Jing, an assistant professor of mechanical engineering and co-corresponding author of the study, developed the ultrasound technology.

According to Jing, each PLGA nanoparticle is given either a positive or negative charge. The positively charged coating is comprised of a biocompatible material commonly found in shrimp cells called Chitosan. The negatively charged coating is biocompatible as well, but found in a type of seaweed called alginate. 

A nano-network is formed as the positively and negatively charged coatings are attracted to each other. The nano-network is injected into the layer below the skin called the subcutaneous layer and holds the nanoparticles together to prevent them from dispersing randomly throughout the body, according to Jing.

According to Gu, the nanoparticles are porous but once they are in the patient’s body, the insulin begins to diffuse from within the nanoparticles. The majority of the insulin from within the particle doesn’t travel far, the insulin remains suspended in a de facto reservoir created by the electrostatic force of the nano-network. These factors create an insulin dose that will be administered into the bloodstream as needed. 

Insulin is a hormone that transports glucose from the bloodstream to the body’s cells. Diabetic patients require additional glucose to maintain healthy glucose levels. At the moment diabetic patients inject insulin into their bloodstream multiple times a day to maintain healthy glucose levels. 

Multiple injects a day can be inconvenient and painful for some patients.

“This new technology has the potential to eliminate the need for multiple injections a day,” Gu said. 

Thanks to the technology developed by Gu and his team of researchers, the insulin is already in a patient’s body and ready for them to use. Patients would use a small ultrasound device where their nano-network is located to release the insulin from the de facto reservoir into their bloodstream.

Gu and his team of researchers theorize that their technique works due to the effect of the ultrasound wave on the microscopic gas bubbles in the tissue. When the ultrasound waves excite the gas bubbles it causes a temporary disruption in the nano-network that pushes the nanoparticles apart, which weakens to the electrostatic force found by exerted on the reservoir. The process allows the insulin to enter a patient’s bloodstream, and at an accelerated rate, due to the ultrasound waves pushing the insulin.

“When the patient removes the ultrasound device from the site of the nano-network, the electrostatic force is reestablished to pull the positively or negatively charged nanoparticles back together,” Jing said. “From there the nanoparticles will diffuse more insulin which will refill the reservoir.”

According to Gu, proof-of-concept testing has been done on laboratory mice with Type 1 diabetes and found that the technique achieves a quick release of insulin into the bloodstream. The nano-network has the capacity to contain enough insulin to regulate a patient’s glucose levels for up to ten days, Gu said.  After the ten day period patients will need to inject a new nano-network while the previous one dissolves and absorbs into the body.

According to Gu, the research is currently at the small animal testing stage. Researchers are focusing their efforts on mice- based studies. 

“It may take a few years for this technology become available to the public,” Gu said. “Before we begin clinical trials we will perform large animal (pig based) studies.”