The key to better drug delivery could be the crustacean.

N.C. State University researchers have developed a way to use material from shrimp and crab shells to create a sponge-like vessel that can better deliver a drug in the human body. The first target is insulin delivery for diabetes but the research could have applications for improving drug delivery for other diseases as well.

But why shrimp and crab shells? These shells have a material called chitosan that is biocompatible and easily breaks down in the body, explained Zhen Gu, an assistant professor in the joint biomedical engineering program at N.C. State and the University of North Carolina at Chapel Hill.

The researchers use the chitosan to make a sphere-like matrix to surround the insulin. Insulin, which regulates glucose levels in the blood, is produced in the pancreas by cells called beta cells. In type 1 diabetes, the pancreas fails to produce enough insulin. Diabetics need frequent injections of the hormone to regulate glucose levels. Administering insulin with this chitosan sponge could mean less frequent insulin injections for patients.

“The general idea is to achieve a formulation that can mimic the function of beta cells,” Gu said.

Why crab and shrimp shells?

At approximately 250 micrometers in size, the chitosan sponge is small enough to be injected into a patient. The matrix surrounds the insulin, ready to deliver it into the bloodstream. The second answer to the question of “Why chitosan?” is chemistry. This chitosan matrix also has smaller nanocapsules made of a porous polymer that contains glucose oxidase or catalase enzymes. When a diabetic patient’s blood sugar rises, the glucose triggers a reaction that causes the nanocapsules’ enzymes to release hydrogen ions. It’s these ions that trigger the chitosan sponge to release the insulin that it has been carrying.

The ions bind to the molecular strands of the chitosan sponge, giving them a positive charge. Like charges repel. So the strands of the positively charged chitosan matrix push away from each other, opening gaps that release the insulin into the bloodstream. As the insulin begins its work of reducing glucose levels in the body, the chitosan loses its positive charge. The chitosan strands come back together, retaining the remaining insulin. Because this technology has the ability to not only deliver the insulin but also regulate insulin levels in the body, the researchers have dubbed it a “smart sponge.”

The sponge responds quickly in an acidic environment, which could lead to applications that don’t require use of the additional enzymes to trigger the chitosan matrix to release a drug. For example, tumors are acidic and have high concentrations of hydrogen ions. A smart sponge carrying cancer drugs could release its payload when triggered by contact with the hydrogen ions.

More research

Administering new drugs using this new technology is still years away. Gu said that while the researchers have demonstrated the technology successfully in studies involving mice, additional studies in larger animals are needed before moving into clinical trials in humans. But Gu said he has already been in contact with pharmaceutical companies interested in the research so far and eager to see how the additional studies progress.

“We don’t want to rush to perform the clinical trials,” Gu said. “It’s difficult to predict but (clinical trials are) definitely a couple of years away.”

The research was published online in ACS Nano. The research was supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust Foundation and a gift from the Tayebati Family Foundation.

Gu’s research team includes Daniel Anderson, the senior author of the research paper and an associate professor of chemical engineering and member of the Koch Institute for Integrative Cancer Research at MIT, and researchers from the Department of Anesthesiology at Boston Children’s Hospital. Gu began his work in this drug delivery research two years ago when he was a research fellow at MIT and the Harvard Medical School working in Anderson’s lab.