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Drug-Delivering Wire Streamlines Tuberculosis Treatment

The new drug wire, tested in a pig stomach, delivers measured doses of tuberculosis drugs. | Diana Saville

Researchers have created a retrievable, wire-like device that safely resides in the stomach and releases large dosages of drugs over several weeks. The technology, which was successfully tested in pigs, is detailed in a new study in the March 13 issue of Science Translational Medicine.

The delivery system could help patients in remote and resource-constrained geographic areas adhere to complicated drug treatments for infectious diseases such as tuberculosis and hepatitis, which are currently treated with burdensome amounts of oral medications.

Tuberculosis, a bacterial infection that damages the lungs, is one of the most widespread and devastating infectious diseases today. According to the Centers for Disease Control and Prevention, there were approximately 10 million cases of tuberculosis and 1.3 million related deaths worldwide in 2017.

The disease is particularly devastating in developing countries that lack healthcare resources. Over 95% of cases and deaths occur in developing regions, and eight countries — including India, China, and Nigeria — account for two-thirds of new tuberculosis cases, according to the World Health Organization.

Most cases of tuberculosis can be effectively treated with antibiotics, but treatment plans often require taking cumbersome amounts of oral medications. The current standard of care is called directly observed treatment, short course or DOTS, which involves coming into a clinic daily and taking multiple drugs, sometimes for several months. According to the study authors, an average 60-kilogram (132-pound) patient must take 3.3 grams of antibiotics a day, a dose that exceeds the largest available oral capsule.

Following DOTS treatment regimens can be challenging for patients, as previous research has reported that 50% of patients experience difficulty with sticking to treatment recommendations. This is particularly true in developing regions that lack infrastructure, where it may be more difficult to consistently access the right doses of medications.

Poor patient adherence to treatments has therefore become a major contributor to treatment failure and the emergence of drug-resistant tuberculosis strains, according to Giovanni Traverso, assistant professor at Harvard Medical School and a senior author of the new study.

"We were motivated by the tremendous problem of medication nonadherence," he said. "The long and frequent dosing regimen [for tuberculosis] with daily clinic visits is a huge burden for the patients and health care system."

"As engineers, we are trying to address this challenge by reducing the frequency that patients would need to come to the clinic," he added.

To meet the need for a more practical delivery system, Malvika Verma, a Ph.D. candidate at MIT, and colleagues developed a new delivery platform that releases drugs directly into the stomach over long periods of time. Their device consists of a flexible wire that houses up to 600 bead-like drug pills, which can be deployed to the stomach through the esophagus in 60 seconds.

After reaching the stomach, the wire is designed to uncoil and continuously releases grams of drugs over several weeks. Once treatment is completed, it can be quickly retrieved with a nasogastric tube, a tube that is inserted through the nose and past the throat.

The team tested their device by loading it with antibiotics that are commonly used against tuberculosis and inserted it into healthy pigs. They found that the wire safely released the standard tuberculosis antibiotics rifampicin over one week and doxycycline hyclate over four weeks and was easily retrieved after the treatment was completed.

"This is the first example of a large dose depot system capable of extended drug release," said Traverso. "In general, drug depots hold an order of magnitude less drug than [our device], and therefore we can start to address unmet needs in treating tuberculosis."

To assess the feasibility of their device, they conducted a questionnaire of 111 tuberculosis health care providers and 300 patients with tuberculosis in India. Their survey revealed that most patients would be willing to undergo a nasogastric tube procedure, and a long-term nasogastric drug delivery system was considered feasible on the ground.

One economic model predicted that such a device could result in more than $8,000 in healthcare savings per patient annually. These savings would arise because maximizing adherence to the regimen could prevent the development of antibiotic-resistant tuberculosis strains, which are more difficult and expensive to treat, according to Traverso. Furthermore, the patient could also save money by going to a clinic once a month instead of daily, and keep going to work or school, he said.

To translate their approach into humans, the scientists plan to conduct more preclinical studies in animals such as dogs, which have a similar stomach environment compared to humans. They are working with their collaborators in India to further understand how feasible and acceptable their platform would be for patients.

The team is also investigating whether the system could be used to administer drugs for other conditions, said Traverso. They are currently developing a version that could be used to treat hepatitis C, another disease where drug adherence is a challenge, and designed the system to be applicable with a variety of different pills and medications.

[Credit for associated image: Malvika Verma, Feyisope Eweje, John A. F. Salama, Jonathan B. Miller]