Sound way to deliver medicine

Drugs administered alongside a blast of ultrasound waves are over twenty times better absorbed, a new study has shown.
20 October 2015

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Drugs administered alongside a blast of ultrasound waves are over twenty times better absorbed, a new study has shown.

Many medicines are given by mouth, but other drugs are unsuitable for oral administration and require significant modification before they can be given this way.Ultrasound

Now a team at MIT, in the US, have shown that combining simple ultrasound with the drug might make this unnecessary.

Moreover, the ultrasound exposure made it possible for agents like insulin, which are not normally absorbed intestinally, to enter the bloodstream.

Working initially with mice and pigs, Carl Schoellhammer and his colleagues, writing in Science Translational Medicine, showed that large molecules like glucose, insulin and the drug mesalazine, which is used to treat inflammatory bowel disease, could be absorbed up to twenty-two fold more efficiently when a small probe delivering soundwaves at between 20 and 40kHz was used internally for a minute afterwards.

Critically, only very minor disruption to the surface lining of the bowel was seen after two weeks of exposure to the technique in a group of pigs. The technique works, they suggest, by initiating what's called "cavitation" at the site of the ultrasound delivery.

This is where small bubbles rapidly pop into existence and then burst, unleashing a wave of energy. This, it seems, can make the lining of the intestine temporarily more porous to drugs.

To find out whether the effect would translate into a clinical benefit, the team also tested it on a group of mice with acute intestinal inflammation resembling the human conditions Crohns and ulcerative colitis.

Mesalazine therapy combined with ultrasound resulted in animals with intestinal linings that were indistinguishable from healthy control mice.

Animals given just the drug and no ultrasound, on the other hand, continued to show signs of inflammation.

The MIT team acknowledge that the agents, and the ultrasound, need to be administered via the rectum, but they point out that this is currently standard practice patients undergoing treatments for inflammatory bowel disease.

More exciting, though, is the prospect of shrinking the technology to microscope proportions so that everything - drugs and ultrasound, can be swallowed.

"Our technology could be miniaturised to dimensions compatible with ingestion," the team say, "allowing for ingestible sound-emitting capsules for systemic delivery."

The next step, however, will be to test the effectiveness of the approach in human patients while also checking that it is safe and that there are no side effects of rendering the intestinal wall tempoararily more permeable in this way.

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