Drug delivery system would allow patients to switch from daily to monthly doses — ScienceDaily

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Tuberculosis is one of the world's deadliest infectious diseases: one third of the world's population is infected with tuberculosis, and more than 1 million people die each year from the disease.

One reason why tuberculosis is so common is that treatment requires six months of antibiotics per day, and about half of them are difficult to maintain, especially in rural areas where medical facilities are limited. To solve this problem, a research team led by the Massachusetts Institute of Technology designed a new antibiotic treatment that they hope will make it easier to cure more patients and lower healthcare costs.

Using this new method, a coiled line containing antibiotics is inserted into the stomach of a patient through a nasogastric tube. Once in the stomach, the device slowly releases antibiotics within a month, eliminating the need for patients to take the drug every day.

Giovanni Traverso, an assistant professor of mechanical engineering at the Massachusetts Institute of Technology, and a gastroenterologist at Brigham and Women's Hospital, said: "Having a system that ensures patients receive a complete treatment can be truly transformative." When you think about tuberculosis, you have to take more grams of antibiotics every day for months, and we need another solution."

Traverso and Professor of the Massachusetts Institute of Technology's David H. Koch Institute, Robert Lange, are senior authors of the study, published in the March 19th issue of Scientific Translational Medicine including complete List of authors. . The first author of the paper is Malvika Verma, a graduate student at the Massachusetts Institute of Technology; the team includes other members of the Massachusetts Institute of Technology, as well as Harvard Medical School, Boston University School of Public Health, several hospitals in India, and the Mumbai Tata Trust in India. Researcher.

Long-term delivery

For several years, Traverso and Langer have been studying various pills and capsules that can be left in the stomach and slowly released after swallowing. They believe that this drug delivery can improve the treatment of many chronic diseases that require daily medication.

One of their capsules has shown hope for a small amount of medication to treat HIV and malaria. After swallowing, the outer coating of the capsule dissolves, allowing six arms to expand, helping the device into the stomach. For example, the device can carry about 300 mg of the drug – enough for a week of HIV treatment. However, it is far less than the payload required to treat tuberculosis, requiring about 3 grams of antibiotics per day.

"We must develop a completely new system that automatically releases these drugs in about a month," Verma said. "This new system can hold more drugs, it can release drugs for a long time."

The new device is a thin elastic wire made of Nitinol – Nitinol can change its shape depending on the temperature. Researchers can string up to 600 "pill" antibiotics on wires and package them in polymers. The composition of these polymers can be adjusted to control the rate at which drugs are released into the stomach.

The wires are delivered to the patient's stomach through a tube that is inserted into the nose and are typically used in hospitals to provide medications and nutrients. As part of their research, the researchers interviewed 300 tuberculosis patients in India, and most said the birth was acceptable for their long-term treatment.

"In many cases, patients prefer this situation, and patients may have health care every two weeks or every four weeks, rather than being seen by health care providers every day," Traverso said.

Once the wire reaches a higher temperature in the stomach, it forms a coil that prevents it from passing further through the digestive system. In the pig test, the researchers found that their prototype device could release several different antibiotics at a constant rate for 28 days. Once all of the drug has been delivered, the device is removed through the nasogastric tube using a magnet that attracts the coil.

Reducing costs

The research team includes David Collins, an economist at Boston University, who analyzed the potential economic impact of the treatment. He found that if implemented in India, the cost of treatment for each patient could be reduced by about $8,000.

"The current TB treatment model is direct observation of treatment, short-term treatment, patients must come in every day, let someone watch them take medicine. This is a huge burden for patients and the health care system," Verma said. “We envision this as an infrastructure that uses direct observation therapy, but reduces the frequency of treatment from daily to monthly.”

Another disease that may be useful in this method is hepatitis C, which requires treatment with antiviral drugs for 2 to 6 months. Many other infectious diseases also require too much drug dose to be suitable for one of the smaller ingestible devices developed by Traverso and Langer.

"In many cases, patients need to take multiple doses of the drug, but so far this is difficult to do," Lange said. “We believe this new approach is an important milestone in solving this problem.”

The researchers say the system is also useful for providing drugs that can treat alcohol addiction and other types of drug abuse.

The study was funded by the Bill and Melinda Gates Foundation, the National Institutes of Health, the Massachusetts Institute of Technology Tata Center, the National Science Foundation, the Alexander von Humboldt Foundation, and the Brigham and Women's Hospital. .


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