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Researchers develop an injectable, long-acting medication delivery method for tuberculosis

Research on animal models, which was reported in the journal Nature Communications, suggested the possibility of treating TB with a single injection that lasts at least four months as opposed to the current standard of care, which necessitates strict adherence to a daily medication regimen.

More than 1.5 million people worldwide passed away from TB in 2020, which was the first time this has happened in more than ten years and highlights the need for improved access to treatments on a global scale.

A long-acting injectable version of the anti-TB medication rifabutin was created by researchers at the UNC School of Medicine, the UNC Institute for Global Health and Infectious Diseases, and the International Center for the Advancement of Translational Science.

“We think our approach could dramatically change TB treatment,” said Martina Kovarova, PhD, associate professor of medicine at UNC “Affordable long-acting formulations with generic anti-TB drugs would help ease the burden of this disease on low-income communities around the world where better access to treatment is most needed.”

Co-author Miriam Braunstein, Ph.D., professor of Microbiology and Immunology at the UNC School of Medicine and member of the UNC Institute for Global Health and Infectious Diseases, added, “During the COVID-19 pandemic, we witnessed more deaths due to TB because of disruption or reallocation of health services, setting us back at least five to eight years in the global fight against TB. We think long-acting formulations could be a game-changer, whether it’s for preventative therapy or treatment of disease.”

The World Health Organization estimates that about one-quarter of the planet’s population has a latent TB infection with the possibility to reactivate, which can cause symptoms like weakness, weight loss, fever, coughing up blood, and chest pain.

Tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), affects an estimated 10 million people annually. Drug resistance and treatment failure might result from not following strict medication regimens. To address this, UNC researchers worked to develop a therapeutic delivery system that would offer a practical means of enhancing medicine adherence.

Experiments were conducted to mix rifabutin with biodegradable polymers and non-toxic solvents that solidify in the body following subcutaneous injection by Manse Kim, Ph.D., a postdoctoral researcher at UNC-Chapel Hill, and UNC graduate student Claire Johnson. The amount of rifabutin that could be incorporated was also greatly increased by the addition of a substance by the researchers.

The scientists used mice models to study how the cemented implant gradually dissolved over the course of 16 weeks, continuously releasing its pharmacological payload. Mice exposed to TB were protected from infection with this long-acting formulation. In addition, in mice that had already been exposed to TB, a single injection completely eradicated the virus from the lungs and other tissues. The implant is detachable if any unwanted effects do develop, however the researchers saw no negative effects in the animals.

The FDA has previously given its approval for the use of this kind of long-acting technology for treating cancer, schizophrenia, and opioid dependence.

“We think this technology could be leveraged in our battle against tuberculosis worldwide,” Kovarova said. “More research is needed before phase 1 trials in humans, but our study provides an important step toward a much-needed long-acting treatment and prevention strategy against TB.”

Researchers develop an injectable, long-acting medication delivery method for tuberculosis

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