Capsules are designed to inject biologics into the stomach lining.

Ever since insulin was first developed, researchers have been actively seeking a means for achieving oral delivery of this important medicine. As biologic drugs have become increasingly successful, the desire to find an alternative to parenteral delivery has grown in tandem. The challenge has been get these very large, sensitive biomolecules to survive the harsh environment of the stomach and to be absorbed into the bloodstream.

Researchers at Harvard Medical School and the Massachusetts Institute of Technology may have found a way to overcome these challenges. A hollow pill that has its center of mass near a flattened end has been developed by a team headed by gastroenterologist and bioengineer Carlo Giovanni Traverso, and drug delivery expert Robert Langer. With this design, the pill enters the stomach when swallowed, with the flat surface facing the stomach lining. The flat end, made of sugar, dissolves in the stomach, allowing a tiny tensed spring topped with a needle — made from solid insulin — to be released. The needle pokes the outer stomach layer, dissolves, and enters the bloodstream.

When tested in rats and pigs, the pill was observed to deliver similar insulin levels into the blood as a subcutaneous injection. The researchers also confirmed that poking the stomach lining does not appear to lead to any damage, although more studies are needed to ensure that no long-term health issues might arise. 

Rani Therapeutics has notably taken a slightly different approach. When this pill reaches the small intestine, the pH of the environment causes the generation of carbon dioxide, which inflates a tiny balloon that then presses a needle packed with the drug through the intestinal lining. The company has completed numerous animal studies and, in one safety study with humans, reported that people did not sense the inflation of the balloon. It is now planning clinical trials with octreotide, a drug that treats acromegaly.