For individuals with type 2 diabetes, daily insulin injections are a necessary but uncomfortable routine. A team of researchers at the Massachusetts Institute of Technology (MIT), however, have developed a pill that can deliver doses of insulin, replacing daily injections. Their work was published in the journal Science.
Individuals with type 2 diabetes are unable to regulate their blood sugar levels, due to an inability to produce sufficient amounts of the hormone insulin or to cells’ lack of response to insulin. The hormone is required for glucose in the blood to enter muscle, fat and liver cells, and insulin resistance leads to hyperglycemia, or abnormally high blood glucose levels.
Hyperglycemia, if untreated for a long period of time, can eventually lead to the accumulation of ketones in the blood, leading to a serious condition called ketoacidosis. Symptoms can involve excessive thirst, nausea and fatigue, and the condition is potentially life-threatening. To prevent hyperglycemia, individuals with type 2 diabetes inject insulin daily.
While patients in general typically prefer pills to injections, it is difficult to deliver insulin orally. In the gastrointestinal tract, the protein will be exposed to unfavorable environments including those with extreme pH, large concentrations of protease and cellular tight junctions.
The researchers from MIT designed a pill that would allow oral delivery of insulin. Equipped with a single needle, the pill injects the hormone into the stomach wall. The stomach wall was chosen instead of the intestinal wall, since the former is several times thicker, making the injection safer.
The needle itself has a tip of compressed, freeze-dried insulin, and the rest of the needle is biodegradable.
One major innovation of the pill is its self-orienting capability.
“As soon as you take it, you want the system to self-right so that you can ensure contact with the tissue,” Giovanni Traverso, a corresponding author on the paper, explained in a press release.
When deciding the structure of the pill, the researchers were inspired by the shape of the leopard tortoise. The shell of the tortoise is high, steep and rounded, allowing it to easily upright itself if it is flipped onto its back.
The researchers used a MATLAB program to optimize the shape of the pill, attempting to minimize the time it takes for the pill to orient. They used the shape of the leopard tortoise’s shell as an initial input shape.
Once the pill is oriented, the actual injection happens through a spring mechanism. Inside the pill, the needle is connected to a compressed spring, which is itself connected to a sugar disk. When the sugar is dissolved in the stomach, the spring is released.
The pill was tested in pigs, who were given capsules containing human insulin. After administration, the researchers confirmed that the injection occurred in the proper layer of the stomach and that there was no damage to the tissue. In addition, they monitored the pigs’ blood glucose levels, determining that they lowered after the pill was taken.
Initial experiments showed that while the pill was effective in an empty stomach, food particles and ingested liquids would prevent delivery. The researchers subsequently designed a valved membrane insert to protect the pill from stomach contents.
The pill in its current form is similar in size to other Food and Drug Administration-approved devices, and the materials it uses are also present in other approved ingestible capsules. Going forward, the researchers are interested in monitoring long-term effects of daily injections into the stomach wall, any potential for a foreign body response against the pill and whether exposure of the pill to other drugs in the stomach will affect its activity. However, they are hopeful that this pill design will provide a way to deliver not only insulin but other therapies involving biomacromolecules.