Using ultrasound waves, researchers from MIT and Massachusetts General Hospital (MGH) have found a way to enable ultra-rapid delivery of drugs to the gastrointestinal (GI) tract. 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, the researchers say.
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. To overcome that, the researchers sought a way to stimulate more rapid drug absorption.
"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," Giovanni Traverso, a researcher at MIT and senior senior authors of a paper describing the technique in the journal Science Translational Medicine.
Enhanced delivery The researchers began exploring the possibility of using ultrasound to enhance drug delivery 30 years ago. In 1995, they 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.
Ultrasound improves 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.
In this study, the 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.
They 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.
While inflammatory GI diseases are an obvious first target for this type of drug delivery, it could also be used to administer drugs for colon cancer or infections of the GI tract, the researchers said. They are now performing additional animal studies to help them optimize the ultrasound device and prepare it for testing in human patients.