On the Ridge

Treating Diabetes Without Pain

Every day, millions of Americans with diabetes have to inject themselves with insulin to manage their blood-sugar levels. But less painful alternatives are emerging. Niagara University faculty members and students are developing a new way of administering the medicine orally with tiny vesicles that can deliver insulin where it needs to go without a shot, and have already shared their in vivo testing results.

Mary McCourt, Ph.D., Lawrence Mielnicki, Ph.D., and Jamie Catalano, ’17, presented their work during the summer of 2016 at the 252nd National Meeting & Exposition of the American Chemical Society, the world’s largest scientific society, in Philadelphia. A press conference to explain the results of the NU team was held during the meeting, which features more than 9,000 presentations on a wide range of science topics.

“We have developed a new technology called a Cholestosome™,” said Dr. McCourt, leader of the research team. “A Cholestosome™ is a neutral, lipid-based particle that is capable of doing some very interesting things.”

The biggest obstacle to delivering insulin orally is ushering it through the stomach intact. Proteins such as insulin are no match for the harsh, highly acidic environment of the stomach. They degrade before they get a chance to move into the intestines and then the bloodstreav where they’re needed.

Some efforts have been made to overcome or sidestep this barrier. One approach packages insulin inside a protective polymer coating to shield the protein from stomach acids and is being tested in clinical trials. Another company developed and marketed inhalable insulin, but despite rave reviews from some patients, sales were a flop. Now its future is uncertain.

The Niagara University researchers have a new tactic. Using the patented Cholestosomes™ developed in the B. Thomas Golisano Center for Integrated Sciences, they have successfully encapsulated insulin. The novel vesicles are made of naturally occurring lipid molecules, which are normal building blocks of fats. But the researchers said that they are unlike other lipidbased drug carriers, called liposomes.

“Most liposomes need to be packaged in a polymer coating for protection,” said Dr. Mielnicki. “Here, we’re just using simple lipid esters to make vesicles with the drug molecules inside.”

Computer modeling showed that once the lipids are assembled into spheres, they form neutral particles resistant to attack from stomach acids. Drugs can be loaded inside, and the tiny packages can pass through the stomach without degrading. When Cholestosomes™ reach the intestines, the body recognizes them as something to be absorbed. The vesicles pass through the intestines, into the bloodstream, and then cells take them in and break them apart, releasing insulin.

The team has delivered multiple molecules with these vesicles into cells in the lab. To pack the most insulin into the Cholestosomes™, the researchers determined the optimal pH and ionic strength of the drug-containing solution. They then moved the most promising candidates on to animal testing. Studies with rats showed that certain formulations of Cholestosomes™ loaded with insulin have high bioavailability, which means the vesicles travel into the bloodstream where the insulin needs to be.

Next, the team plans to further optimize the formulations, conduct more animal testing and develop new partnerships to move forward into human trials.