Could treating diabetes someday be as simple as slapping on a patch? A UCLA-led research team thinks so, and it’s seeking FDA permission to prove it.A research team led by UCLA bioengineering professor Zhen Gu claims to have overcome some of the technological hurdles around creating a patch that releases insulin based on the level of glucose in a person’s body.
Their creation is a coin-sized (about 5 cm2), adhesive polymer patch with microneedles. The pyramid-shaped microneedles are about 400 microns wide at the base and 900 microns tall and penetrate the stratum corneum, the outer layer of the skin. When the interstitial fluids in the skin reach hyperglycemic levels, the phenylboronic acid units within the polymer matrix promote swelling of needles and release the insulin preloaded into the matrix.
Because the researchers created the patch through a molding and UV light-curing process that doesn’t damage the insulin, about a fifth of the microneedles’ weight is insulin — enough to enable clinical use, according to the researchers’ paper in the Feb. 3 edition of the journal Nature Biomedical Engineering. Studies showed that the patches maintained the bioactivity of the insulin for more than 8 weeks at room temperature.
“There’s a high amount of insulin inside, and we’re making the whole needle matrix glucose-responsive,” Gu said in a recent interview with Medical Design & Outsourcing.
Controlled studies on diabetic minipigs showed the patches could maintain the pigs’ glucose levels in a normal range for more than 20 hours, according to the paper. Glucose challenges conducted on both diabetic mice and pigs showed the patches could bring down glucose levels within 1 to 2 hours.
Zenomics, the startup Gu co-founded, is applying for FDA approval for a human clinical trial. The biomedical device company MicroPort Scientific Corp. invested $5.8 million in Zenomics in 2017.
“The microneedle patch provides such a convenient, painless way to apply a glucose-responsive insulin delivery system to people with diabetes,” Gu said. “It could potentially enhance the health and quality of life of people with diabetes.”
Gu’s work on smart insulin delivery goes back a decade to his time as a postdoctoral fellow at the Massachusetts Institute of Technology lab of medtech innovator and serial entrepreneur Robert Langer, a co-author of the recent paper and a member of Zenomics’ board. Langer had a grant available for diabetes research, and Gu had some interest in the subject because his grandmother back in China — now passed away — had Type 2 diabetes.
“I understand their pain, and I understand their inconvenience,” Gu said of people with diabetes.
Langer said of Zhen’s work via email: “It has been a pleasure to see the terrific progress by Zhen and his team. It could someday lead to new ways of treating diabetes and other diseases.”
Work continued during the years Gu spent as a biomedical engineering professor at the University of North Carolina at Chapel Hill and North Carolina State University. It was there that he began to collaborate with another paper co-author, Dr. John Buse, whom the American Diabetes Association has recognized for his work on hundreds of clinical studies and dozens of epidemiologic analyses and translational projects.
Buse said of Gu: “He’s the brains of the operation, and I just try and keep him focused on how to develop this into something that works in patients.”
The microneedle patch, according to the paper, boasts some improvements over similar concepts because it doesn’t rely on complicated chemical reactions that could irritate the skin. Because it is non-degradable, a person can remove it entirely after treatment. Gu declined to disclose how they did it, but he and his colleagues also figured out how to incorporate an adhesive without interfering with the microneedles’ ability to deliver insulin.
Buse thinks the patch could provide a potential alternative — or at least a backup — to the continuous glucose monitor/ insulin pump combinations that major medical device companies such as Medtronic, Abbott, Dexcom, Insulet and Tandem Diabetes Care are touting.
“The genius of this is if you could have something that was relatively unobtrusive, like a patch, which fundamentally is like a Band-Aid, and the patch would release insulin in response to glucose levels,” Buse said of Gu’s concept. “You basically would solve the diabetes problem in many ways.”
It’s actually possible to personalize the patches to release varying levels of insulin, either by varying the ratio of the monomers making up the polymer or by changing the size of the patch, according to the paper.
“You might have one that you would wear all day that basically take care of things when you’re not eating a meal. And then you would slap on a big patch because you’re going to have ice cream and cake at a birthday party — or a small patch because you’re going to have a salad,” Buse said.
“We don’t know yet what the patches are going to be capable of,” Buse said. “In an ideal world, it’d be one patch a day or one patch a week. It’s going to take a while before we figure out what’s really possible.”