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Enhancing drug delivery with ultrasound | MIT News

It can be difficult to get drugs to disease sites along the gastrointestinal tract, which includes the mouth, esophagus, stomach, small and large intestines, and anus. Invasive treatments can take hours as patients wait for sufficient amounts of medication to be absorbed into the right place. The same problem is holding back newer treatments such as gene-altering therapies.

Now MIT spinout Suono Bio is advancing a new approach that uses ultrasound to deliver drugs, including nucleic acids such as DNA and RNA, to the gastrointestinal tract more effectively. The company believes its technology can be used to deliver a wide range of therapeutic molecules to the areas of the body that have proven to be the most difficult to treat.

“Ultrasound is a well-known technology that has been used in clinics for decades,” says Suono co-founder and CTO Carl Schoellhammer PhD ’15. “But now we’re doing something really unique and new with it to make it easier to deliver things that couldn’t be delivered before.”

Suono’s technology is the culmination of more than three decades of discoveries in MIT laboratories by researchers like Schoellhammer and Suono’s co-founders, Robert Langer, the David H. Koch Institute professor at MIT, and Giovanni Traverso, an assistant professor at MIT. The platform takes advantage of a phenomenon in which ultrasonic waves create small jets in a liquid that can be used to push drugs into cells.

The company’s first treatment program targets ulcerative colitis. Last week, Suono announced a round of funding to bring this program and others in its pipeline into clinical trials.

Beyond this initial program, the founders say the platform could be used to deliver a range of molecules, from nucleic acids to peptides to larger proteins, into any part of the gastrointestinal tract. And although the first iteration of Suono’s delivery platform will utilize handheld systems, the founders believe the technology could one day be contained in a battery-powered, ingestible pill.

“The [first drug candidate] is the proof of concept where we could potentially solve a very urgent clinical problem and do a lot of good for many patients, ”says Schoellhammer. “But then you reduced the risk of the entire platform because the study applied ultrasound to a mucosal surface and your entire GI tract is one large mucosal surface. All subsequent products that we manufacture, including those in other form factors, will therefore build on one another. “

A discovery with a promise

Schoellhammer was a PhD student in chemical engineering from 2010 to 2015. During this time he was jointly advised by Daniel Blankstein, the Herman P. Meissner Professor of Chemical Engineering, and Langer, who co-founded over 40 companies.

Langer and Blankschtein first discovered in 1995 that ultrasound waves can be used to transport drugs through the skin. When ultrasound waves penetrate a liquid, they create tiny, imploding bubbles that, when burst, create forces that can move drugs into cells before the drugs break down. Almost two decades later, Schoellhammer and colleagues at MIT took this discovery a step further by applying two different ultrasonic waves to the skin at the same time to further increase the cell-penetrating forces.

At the time, Traverso was a gastroenterology fellow at Massachusetts General Hospital and was doing the research portion of his training in Langer’s laboratory. Schoellhammer, Traverso, and others decided to see if ultrasound could improve drug delivery to the GI tract. “It seemed so good on the skin that we thought why not try other parts of the body as well,” recalls Schoellhammer.

Medicines usually need to be encapsulated in a protective layer in order to be released into the body without degradation. For the researchers’ first experiment, they combined raw biological drugs and ultrasonic waves. To her surprise, the drugs were effectively absorbed from the gastrointestinal tract. The method worked for the delivery of proteins, DNA, RNA, and forms of RNA that are used in treatments, such as mRNA and siRNA.

“To make a long story short, we just found that everything worked,” says Schoellhammer. “We could deliver a wide range of drug classes without formulation. The GI tract is designed to absorb, but it generally absorbs small molecules. Everything larger, be it biologics, proteins, gene therapies, are broken down because the gastrointestinal tract is also a very inhospitable environment. It has a low pH and an abundance of proteases and nucleases to chew up all of those molecules. So bringing these types of compounds into the gastrointestinal tract is kind of a holy grail. “

The breakthrough convinced Schoellhammer that the technology could one day improve treatment options for patients, and he continued to work with the Deshpande Center for Technological Innovation, entered the MIT $ 100,000 Entrepreneurship Competition, received funding from The Engine Investment Fund, and took a series from other educational experiences, he says, were an integral part of founding Suono.

“It’s mentors like Bob, mentors like Gio, who are able to take courses at MIT’s Business School, work with MIT’s Technology Licensing Office, and learn from their perspective what they think about protecting Seeking technology and external involvement. ”Groups, support from the Deshpande Center, where we received an early grant; I was also the recipient of the Student award of the Lemelson-MIT program 2015“Says Schoellhammer about the things that have helped him on his entrepreneurial journey. “Without all of these parts, Suono doesn’t exist, and the technology doesn’t exist to hopefully one day reach patients.”

Subsequent research confirmed that the ultrasound delivery method could be used to deliver drugs anywhere along the gastrointestinal tract. It also found that the drugs were absorbed much more efficiently and had more positive effects than treatments that used other delivery methods.

“The breadth of molecules that can be transferred is extremely unusual for a drug delivery technology, so that’s really exciting,” says Traverso. “These observations are further supported by the recoveries we saw using ultrasound in GI disease models.”

Come to the patient

Suono expects to begin clinical trials in the next 12 to 18 months. The founders believe that approval of a single drug not only confirms the effectiveness of their approach, but also simplifies regulatory hurdles for future drugs, even if subsequent treatments look very different from those given today.

“Ultrasound can be packaged in many different form factors, such as an enema system, an endoscope, or a pill,” says Traverso. “Using ultrasound in all of these ways opens up many new possibilities. The work now is to identify the best opportunities as so many things could be done. “

In addition to inflammatory bowel disease, Suono is researching treatments for many other gastrointestinal disorders. For example, the localized delivery platform could make the treatment of certain types of cancer more precise and effective.

“Like every company, we have to think carefully about the logical leading indication,” says Schoellhammer. “So let’s start fighting ulcerative colitis. But we don’t end there. This will add value to the entire platform, which one day will be fully ingestible systems for the oral delivery of everything: oral delivery of biologics, oral delivery of nucleic acids. It is this long-term vision that we are focusing on with this path. “

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