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Study could help develop new oral medicines

Researchers examined the digestion of particles in rat intestines, providing insights into oral drug delivery

A sustained-release insulin pill — which would release insulin over a longer period of time as opposed to in spurts — is one step closer to fruition, thanks to research from the University’s department of molecular pharmacology, physiology and biotechnology. 

The research revealed the gut is more capable of absorbing small particles than previously thought. The findings — published Aug. 20 in the Proceedings of the National Academy of Sciences — could allow oral drug delivery for medications that are currently only available in injectable form. This could make it easier for diabetics to take insulin, allowing them to swallow a pill rather than injecting themselves at regular intervals.

“Our digestive systems are designed to break down proteins,” said Daniel Cho ’07 PhD’12 MD’15, one of the study’s authors. But these same systems also break down life-saving drugs such as insulin.

The study examined how microspheres — particles a fraction the size of cells but still far larger than drug molecules — were absorbed in rat intestines. Rats were chosen because they have similar intestinal characteristics to humans, Cho said.

Using electron microscopy, the authors could see the particles after they were absorbed. They also could quantify which organs the particles reached and how long they took to get there — findings that could be significant for other studies on how the body processes nanoparticles, Cho said.

Finally, the researchers studied how the particles were absorbed by administering drugs that blocked certain absorption mechanisms. They tested four drugs that inhibited the absorption pathway known as endocytosis, in which one cell engulfs another substance. They found that all four drugs tested reduced absorption of the microspheres, pointing to endocytosis as the major absorption pathway in the intestine.

The findings could “have great impact on the overall process of drug discovery, development and delivery,” Chong-Su Cho, a research associate at Seoul National University of Korea, who was not involved in the study, wrote in an email to The Herald.

The results challenge the traditional notion that large particles are only engulfed by cells in specific regions of the intestine, he wrote. Only a small portion of intestinal cells are capable of the mechanism, called phagocytosis, making them “difficult” to target for drug delivery, the study’s authors wrote.

Chong-Su Cho indicated that additional insight into the mechanism is necessary before this knowledge can be applied to drug delivery in humans. He said other barriers remain, such as protein drugs degrading while the microsphere is made.

Encapsulating drugs in small biodegradable spheres could “protect a protein from the harsh environment” of the intestine, Daniel Cho said.

If developed, microspheres could aid patients by allowing “controlled and sustained release” of drugs that would be “otherwise rapidly destroyed,” he wrote.

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