Ultrasound delivery

Researchers at MIT and MGH enable ultra-rapid delivery of drugs to the GI tract using ultrasound waves

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CAMBRIDGE, Mass.—Researchers from the Massachusetts Institute of Technology (MIT) and Massachusetts General Hospital (MGH) have found a way to enable ultra-rapid delivery of drugs to the gastrointestinal (GI) tract using ultrasound waves. The study’s lead author is Carl Schoellhammer, a graduate student in chemical engineering who won the $15,000 Lemelson-MIT “Cure it!” Student Prize for this research and for a microneedle pill that delivers drugs directly into GI tissue. The research team also reached the finals of the MIT $100K Entrepreneurship Competition.
Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, is a senior author of the paper. Langer began exploring the possibility of using ultrasound to enhance drug delivery 30 years ago. In 1995, he and Daniel Blankschtein reported in Science that ultrasound could enable delivery of drugs through the skin, but until now it had not been explored in the GI tract. Blankschtein is a Hermann P. Meissner Professor in Chemical Engineering and also a senior author of the paper describing the technique in the Oct. 21 issue of Science Translational Medicine. Schoellhammer tells DDNews that the ultrasound device uses low-frequency ultrasound (<100 kHz) to improve drug delivery by a mechanism known as transient cavitation. When a fluid is exposed to sound waves, the waves induce the formation of tiny bubbles that implode and create microjets that can penetrate and push medication into tissue.
“With additional research, our technology could prove invaluable in both clinical and research settings, enabling improved therapies and expansion of research techniques applied to the GI tract. It demonstrates for the first time the active administration of drugs, including biologics, through the GI tract,” says Blankschtein.
In this study, researchers first tested their new approach in the pig GI tract, where they found that applying ultrasound greatly increased absorption of both insulin, a large protein, and mesalamine, a smaller molecule often used to treat colitis. Schoellhammer says one minute of ultrasound enables 20 times more drug delivered compared to delivery without ultrasound in the testing of small molecules. In the case of biologics and large molecules, ultrasound enables their delivery—without ultrasound, these drugs are not absorbed at all.
This approach could make it easier to deliver drugs to patients suffering from GI disorders such as inflammatory bowel disease, ulcerative colitis and Crohn’s disease. Currently, such diseases are usually treated with drugs administered as an enema, which must be maintained in the colon for hours while the drug is absorbed. However, this can be difficult for patients who are suffering from diarrhea and incontinence.
“We’re not changing how you administer the drug. What we are changing is the amount of time that the formulation needs to be there, because we’re accelerating how the drug enters the tissue,” according to Giovanni Traverso, a research affiliate at MIT’s Koch Institute for Integrative Cancer Research, a gastroenterologist at MGH and one of the senior authors of the paper.
The researchers next investigated whether ultrasound-enhanced drug delivery could effectively treat disease in animals. In tests of mice, the researchers found that they could resolve colitis symptoms by delivering mesalamine followed by one second of ultrasound every day for two weeks. Giving this treatment every other day also helped, but delivering the drug without ultrasound had no effect. They also showed that ultrasound-enhanced delivery of insulin effectively lowered blood sugar levels in pigs.
The researchers are now performing additional animal studies to help them optimize the ultrasound device and prepare it for testing in human patients. Schoellhammer tells DDNews that the researchers are currently testing efficacy of the ultrasound device in a pig model of colitis. The researchers are also testing the device in other disease models and demonstrating the delivery of a wider range of therapeutics, including nucleotide-based molecules. The researchers hope to begin clinical testing in two to five years.
Inflammatory GI diseases are an obvious first target for ultrasound drug delivery, but the ultrasound technique could also be used to administer drugs for colon cancer or infections of the GI tract. “Demonstrating delivery of molecules with a wide range of sizes, including active biologics, underscores the potentially broad areas in which this technology could be applied,” says Schoellhammer. “The ultrasound is a platform technology capable of delivering a wide range of drugs.”

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