Technology could aid in elimination of malaria and treatment of many other diseases.
Researchers at MIT and Brigham and Women’s Hospital have developed a new drug capsule that remains in the stomach for up to two weeks after being swallowed, gradually releasing its drug payload. This type of drug delivery could replace inconvenient regimens that require repeated doses, which would help to overcome one of the major obstacles to treating and potentially eliminating diseases such as malaria.
In a study described in the Nov. 16 issue of Science Translational Medicine, the researchers used this approach to deliver a drug called ivermectin, which they believe could aid in malaria elimination efforts. However, this approach could be applicable to many other diseases, says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.
“Until now, oral drugs would almost never last for more than a day,” Langer says. “This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.”
Langer and Giovanni Traverso, a research affiliate at the Koch Institute and a gastroenterologist and biomedical engineer at Brigham and Women’s Hospital, are the senior authors of the paper. The paper’s lead authors are former MIT postdoc Andrew Bellinger, MIT postdoc Mousa Jafari, and former MIT postdocs Tyler Grant and Shiyi Zhang. The team also includes researchers from Harvard University, Imperial College London, and the Institute for Disease Modeling in Bellevue, Washington.
The research has led to the launching of Lyndra, a Cambridge-based company that is developing the technology with a focus on diseases for which patients would benefit the most from sustained drug delivery, including neuropsychiatric disorders, HIV, diabetes, and epilepsy.
Drugs taken orally tend to work for a limited time because they pass rapidly through the body and are exposed to harsh environments in the stomach and intestines. Langer’s lab has been working for several years to overcome this challenge, with an initial focus on malaria and ivermectin, which kills any mosquito that bites a person who is taking the drug. This can greatly reduce the transmission of malaria and other mosquito-borne illnesses.
The team envisions that long-term delivery of ivermectin could help with malaria elimination campaigns based on mass drug administration — the treatment of an entire population, whether infected or not, in an area where a disease is common. In this scenario, ivermectin would be paired with the antimalaria drug artemisinin.
“Getting patients to take medicine day after day after day is really challenging,” says Bellinger, now a cardiologist at Brigham and Women’s Hospital and chief scientific officer at Lyndra. “If the medicine could be effective for a long period of time, you could radically improve the efficacy of your mass drug administration campaigns.”
To achieve ultra-long-term delivery, drugs need to be packaged in a capsule that is stable enough to survive the harsh environment of the stomach and can release its contents over time. Once the drug is released, the capsule must break down and pass safely through the digestive tract.
Working with those criteria in mind, the team designed a star-shaped structure with six arms that can be folded inward and encased in a smooth capsule. Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down.
After the capsule is swallowed, acid in the stomach dissolves the outer layer of the capsule, allowing the six arms to unfold. Once the star expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract.
“When the star opens up inside the stomach, it stays inside the stomach for the duration that you need,” says Grant, now a product development engineer at Lyndra.
In tests in pigs, the researchers confirmed that the drug is gradually released over two weeks. The linkers that join the arms to the core then dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract.
“This is a platform into which you can incorporate any drug,” Jafari says. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.”
This type of delivery could also help doctors to run better clinical trials by making it easier for patients to take the drugs, Zhang says. “It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs, because currently a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he says.
The new study includes mathematical modeling done by researchers at Imperial College London and the Institute for Disease Modeling to predict the potential impact of this approach. The models suggest that if this technology were used to deliver ivermectin along with antimalaria treatments to 70 percent of a population in a mass drug administration campaign, disease transmission could be reduced the same amount as if 90 percent were treated with antimalaria treatments alone.
“What we showed is that we stand to significantly amplify the effect of those campaigns,” Traverso says. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.”
Peter Agre, director of the Johns Hopkins Malaria Research Institute, who was not involved in the research, described the new approach as a “remarkable” advance that could improve treatment of malaria and any other disease that requires long-term treatment.
“If you could reduce the frequency of dosing, and one treatment would continue to release medicine until the course is completed, that would be very beneficial,” Agre says.
Researchers led by Traverso are working on developing similar capsules to deliver drugs against other tropical diseases, as well as HIV and tuberculosis.
Learn more: New capsule achieves long-term drug delivery
In mice, device destroyed colorectal tumors and prevented remission after surgery
Approximately one in 20 people will develop colorectal cancer in their lifetime, making it the third-most prevalent form of the disease in the U.S. In Europe, it is the second-most common form of cancer.
The most widely used first line of treatment is surgery, but this can result in incomplete removal of the tumor. Cancer cells can be left behind, potentially leading to recurrence and increased risk of metastasis. Indeed, while many patients remain cancer-free for months or even years after surgery, tumors are known to recur in up to 50 percent of cases.
Conventional therapies used to prevent tumors recurring after surgery do not sufficiently differentiate between healthy and cancerous cells, leading to serious side effects.
In a paper published today in the journal Nature Materials, researchers at MIT describe an adhesive patch that can stick to the tumor site, either before or after surgery, to deliver a triple-combination of drug, gene, and photo (light-based) therapy.
New drug-delivery approach holds potential for treating obesity
Researchers at MIT and Brigham and Women’s Hospital have developed nanoparticles that can deliver antiobesity drugs directly to fat tissue. Overweight mice treated with these nanoparticles lost 10 percent of their body weight over 25 days, without showing any negative side effects.
The drugs work by transforming white adipose tissue, which is made of fat-storing cells, into brown adipose tissue, which burns fat. The drugs also stimulate the growth of new blood vessels in fat tissue, which positively reinforces the nanoparticle targeting and aids in the white-to-brown transformation.
These drugs, which are not FDA-approved to treat obesity, are not new, but the research team developed a new way to deliver them so that they accumulate in fatty tissues, helping to avoid unwanted side effects in other parts of the body.
“The advantage here is now you have a way of targeting it to a particular area and not giving the body systemic effects. You can get the positive effects that you’d want in terms of antiobesity but not the negative ones that sometimes occur,” says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.
Brigham and Women’s Hospital (BWH, “The Brigham”) is the largest hospital of the Longwood Medical and Academic Area in Boston, Massachusetts, USA.
It is Harvard Medical School’s second largest teaching affiliate with 793 beds. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare, the largest healthcare provider in Massachusetts.
In 2009 the BWH Biomedical Research Institute (BRI) received $485 million in research support from all sources. For over a decade, it has been one of the two hospitals receiving the most National Institutes of Health (NIH) funding among independent hospitals in the United States. It employs over 3,300 researchers.
BRI has worked on regenerative medicine, designing nanoparticles to attack different types of cancer, and starting a clinical trial for a type of Alzheimer’s disease vaccine. BWH research also includes population studies including the Nurses’ Health Study and Physicians’ Health Study.
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New tablet attaches to the lining of the GI tract, resists being pulled away
Researchers have created a new type of dual-sided pill that attaches to the gastrointestinal tract. The tablet is engineered so that one side adheres to tissue, while the other repels food and liquids that would otherwise pull it away from the attachment site. Such extended-release pills could be used to reduce the dosage frequency of some drugs, the researchers say.