Insulin Formulated as Liquid for Capsule Delivery

Insulin formulated into capsules (Harvard University)

26 June 2018. An bioengineering team created a process to formulate insulin, needed regularly by people with diabetes, as a liquid, to be taken in capsules rather than injections. Researchers from Harvard University describe their process in yesterday’s issue of the Proceedings of the National Academy of Sciences (paid subscription required).

Insulin, needed daily by people with diabetes, is available today mainly as injections. Diabetes is a chronic disorder where the pancreas does not create enough insulin to process the sugar glucose to flow into the blood stream and cells for energy in the body. In type 2 diabetes, which accounts for at least 90 percent of all diabetes cases, the pancreas produces some but not enough insulin, or the body cannot process insulin. Type 1 diabetes is an inherited autoimmune disorder where the body does not produce insulin, and is diagnosed primarily in children or young adults. Centers for Disease Control and Prevention says diabetes affects 30.3 million people in the U.S., with International Diabetes Federation estimating diabetes affects 425 million people worldwide.

A team from the drug delivery lab led by Samir Mitragotri is seeking more convenient ways to take insulin than injections for people with diabetes. Even with injections readily available and new automated insulin pumps now on the market, an oral drug says Mitragotri, would still be a big improvement. He notes in a university statement that, “many people fail to adhere to that regimen due to pain, phobia of needles, and the interference with normal activities. The consequences of the resulting poor glycemic control can lead to serious health complications.”

Insulin and other protein-based biologic drugs face obstacles as oral drugs, since they can be disrupted by acids and enzymes in the gastrointestinal tract. Mitragotri’s group studies ionic liquids as a way to bypass these obstacles. Ionic liquids are salt materials that form a liquid state below the boiling point, 100 degrees C, and are often used in industry as solvents, electrolytes, and lubricants. For drug delivery, ionic liquids must be also be safe for recipients and not impede their cargoes, in this case insulin. To meet these requirements, the team designed an ionic liquid from natural materials — choline, an essential nutrient found in foods and taken as a supplement, and geranic acid, found in herbs and spices including cardamom and lemongrass.

In tests with lab rats, the researchers first injected the ionic liquid-protected insulin into the animals’ small intestines, and found low doses could measurably reduce blood glucose levels for up to 12 hours. The team then filled capsules with a protective coating of chemically inert enteric polymers to protect against degradation by stomach acids. In lab rats, the coated capsules reduced and sustained blood glucose levels by as much as 45 percent.

The researchers also tracked the progress of the protected insulin in the animals, and found it could penetrate the mucous membranes lining the intestines and tightly packed cells in the intestinal walls. In addition, ionic liquid-protected insulin remained stable at room temperature for two months, and lasted for four months under refrigeration. The team plans further preclinical testing with animals for bioavailability and potential toxic effects.

The university adds the researchers’ one-step production process can be scaled up for manufacturing at relatively low cost. The technology is available for licensing and commercialization from Harvard’s Office of Technology Development.

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