Take intensive medication without the needle

MIT researchers discover how medications administered through injections may be taken orally in future treatments of diseases like cancer and diabetes

Imagine cancer patients not having to go to the hospital for hours of chemotherapy. What if, instead, they could just take a pill the way most people take ibuprofen when having a headache?

Researchers at the Massachusetts Institute of Technology and Brigham and Women’s Hospital recently published a study suggesting that some drugs injected into the bloodstream may soon be offered orally.

History of the problem
The study, published in Science Translational Medicine on Nov. 27, is what researcher Eric Pridgen, a former MIT graduate student, called a “platform” study.

“It’s sort of an enabling technology that we hope will allow nanoparticles to go from being limited to injections to being able to be given orally,” Pridgen said.

In other words, the results of this study could enable scientists to put many kinds of medications that are currently administered via injection into a pill form — not just insulin, which was the drug studied, but also in a wide variety of other medications.

Currently, many large drugs such as insulin, proteins involved in immune therapies and chemo drugs are too large to be administered through a pill because they are too large to move from the human intestine into the bloodstream. For that reason, many drugs must be injected directly into the bloodstream to have full effects and benefits for patients.

To create a compact pill form of these drugs, researchers first encapsulated the drugs in something called a nanoparticle. Nanoparticles can be defined in many ways, but for this particular use, researchers described them as “tiny biodegradable polymers.” Researcher Robert Langer, who is MIT’s David H. Koch professor and member of the Koch Institute for Integrative Cancer Research, described nanoparticles as being thinner than a human hair — and Pridgen added that they are even much smaller than a cell.

From this step, the researchers were able to easily insert the nanoparticles into a pill. The problem with this, however, was that the nanoparticles, despite their small size, were still too large to pass through the lining of the intestines.

The lining is composed of epithelial cells that join together and create an impenetrable wall. Breaking this wall would allow the drug-filled nanoparticles through, but could also allow harmful bacteria in.

A new approach
In order to get the drug-harboring nanoparticles into the bloodstream, researchers analyzed a previous study that described how infants absorb antibodies from their mothers’ milk.

There is a cell surface receptor called the FcRN that acts as a sort of keyhole to the bloodstream. Antibodies containing Fc proteins work as the key: when the Fc proteins and FcRN receptor come into contact, the protein is allowed through the intestinal wall and into the bloodstream.

The researchers coated the nanoparticles in Fc proteins, something that had not been tried before, and tested the pills on mice. The results showed a success — the nanoparticles were finally able to reach the bloodstream 11-fold, more efficiently than those that were not.

How it works
Once the nanoparticles enter the bloodstream, they will circulate with the blood until they finally reach a “leaky” blood vessel.

“Normally, in a typical tissue, the blood vessels will grow within the tissue and they’ll be well-formed and they’ll be tight,” Pridgen said.

He said vessels that form in tumors are “a little bit leakier … if you make a nanoparticle of a certain size, it’ll be big enough where it doesn’t leak out of the normal vessels, but small enough that it can leak out into the tumor tissue.”

For this reason, chemotherapy drugs administered using nanoparticles have been heavily studied.

For many cancer patients, treatment means regular trips to a hospital for hours of chemotherapy treatment. Not only is this treatment time-consuming, but it also has a multitude of unpleasant side effects since the medication is technically toxic to human cells.

“What you’re trying to do is give enough drug that’s toxic to the cancer cells, but at the same time, you don’t want to kill all your other cells,” said Pridgen.

This is why the nanoparticles could be so useful. If engineered correctly, the chemo drugs will leak into the tumor only, and not throughout the rest of the body. This could lessen the unwanted side effects patients often experience and also allow medical professionals to administer higher doses to patients.

Pridgen noted it is important the that nanoparticles, which are intended for cancer treatment, reach the tumor sites quickly since the drug will begin leaking out of the nanoparticles quickly. If too much of the drug leaks into the bloodstream, patients may experience the same unpleasant side effects as chemotherapy by injection.

“There’s a lot of engineering that goes into, ‘How do you control the release of the drug?’ or ‘What size do you make it?’ or ‘How fast do you want it to get to the tumor?’, things like that,” Pridgen said. “So they’re all sort of parameters that people are working on to try to optimize for different nanoparticles.”

Despite the extensive research into chemo drugs, the idea of this study was to find if a general platform was attainable — that is, with these results, if any drug can be administered orally.

Student reactions
Ultimately, a large part of the reason this study was conducted was to make administering medications easier for both patients and doctors alike.

“If you’re the patient yourself and you have the choice between taking something orally and an injection, what would you do?” Langer said. “Most people would want to take a pill.”

Many students agreed with Langer’s assertion.

“Obviously it’s a worthwhile thing,” said Tyrus Beaucher, a dual-degree junior in the College of Arts and Sciences and School of Management. “My mother had breast cancer. She had to go receive chemo … it’s just a traumatizing process. The fact that they’re able to do it at home, I think is great for families and great for patients.”

College of Communication graduate student Ashley Davis agreed with Beaucher and wondered what other uses the research could have.

“I would be interested to see if it could be used on children,” she said. “It would be interesting to see how widely it was used or if it would be reserved for more specialized kinds of treatment.”

While Langer did say children are a prime example of patients who would rather avoid an injection, Davis wondered if a pill might someday replace regular childhood immunization shots.

However, as with the creation of any new drug, concerns are raised.

“I don’t know what types of drugs exactly these are, but if there’s a possibility for them to have certain side effects, they could be abused,” said Emily Suarez, a junior in the School of Hospitality Administration, though she added that taking pills could lead to a less “abrasive” treatment experience for medical patients.

COM freshman Charmaine Ye said while having treatment at home may help patients maintain a positive outlook, it can also lead to missed doses.

“They might not take their pill … I feel like people might just give up, or they forget,” Ye said. “If you have to go get a shot, it’s an appointment you have to go.”

Despite the negative possibilities, students and researchers all expressed a positive outlook on the nanoparticle pills.

“It’s too early to say what exact disease it’s going to go after,” Pridgen said. “I think what it shows is that targeting the receptor that we went after is a feasible way to overcome the intestinal barrier.”

CORRECTION: An earlier version of this story stated that both David H. Koch and Robert Langer described nanoparticles as being thinner than human hair, when in fact only Robert Langer, who is MIT’s David H. Kock professor, gave this description. An updated version has been made to reflect these changes.