Ultrasound Drug Delivery For Inflammatory Bowel Disease

Patients with inflammatory bowel disease – such as Crohn’s and ulcerative colitis – often receive their medications through drug-based enemas, which can take hours to be fully absorbed by the lining of the colon. In order to try to speed drug delivery for these patients, researchers at the Massachusetts Institute of Technology (MIT), in collaboration with Massachusetts General Hospital (MGH), have provided evidence that ultrasound waves could promote fast absorption of medicines through the gastrointestinal (GI) tract.

As patients with gastrointestinal disorders often suffer debilitating symptoms – including diarrhea and incontinence – maintaining an enema that lasts multiple hours can be an uncomfortable way to receive treatment. Dr. Giovanni Traverso, a gastroenterologist and researcher for both MIT and MGH, and the principal investigator of the study, believes ultrasound therapy could help patients absorb drugs faster.

“We’re not changing how you administer the drug,” said Traverso. “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.” Application of ultrasound seems to be able to increase permeability in the tissue lining the GI tract, allowing for faster delivery of drugs into the bloodstream.

This technique was originally tested in pigs, and was found to be effective at hastening absorption of both small and large molecules, including mesalamine – a drug used to treat colitis – and insulin, respectively. The paper was published in the journal, Science Translational Medicine.

To further test the effect of ultrasound on GI tract absorption, the researchers performed one second of ultrasound following enema delivery of mesalamine in mice, for two weeks. The ultrasound-treated mice were able to absorb the drug faster, and the mesalamine was successful at resolving the symptoms of colitis, while those who were given no ultrasound stimulation showed no change.

The researchers found that administering the ultrasound every other day was also effective. The ultrasound is effective at speeding-up drug absorption because the sound waves create tiny bubbles in the solution. These bubbles implode and form microjets that act to drive the drug into the lining of the colon; this phenomenon is known as transient cavitation.

Though some members of Traverso’s team have previously shown more efficient drug delivery through the skin using ultrasound, this study was the first of its kind to demonstrate the technique’s effectiveness in the GI tract. The team hopes the new technique will not only improve treatment of inflammatory bowel disease, but also certain cancers and infections of the GI tract.

“This technology has great utility in localized as well as systemic delivery of drugs,” said Samir Mitragotri, a professor of systems biology and bioengineering at the University of California-Santa Barbara, and a drug delivery researcher not involved in the current project. The researchers say they plan to conduct additional animal studies in an attempt to optimize the therapy for human use.

Sources:

• Ultrasound may speed up drug delivery in the GI tract – http://www.medicalnewstoday.com/articles/301384.php
• Schoelhammer, C., Schroeder, A., Maa, R., Yves Lauwers, G., Swiston, A., Zervas, M., Barman, R., DiCiccio, A., Brugge, W., et al. (2015). Ultrasound-mediated gastrointestinal drug delivery. Science Translational Medicine, 7 (30).