Scientists Create Long-Acting Injectable Drug Delivery System for Tuberculosis

2020 In 2020, more than 1.5 million people worldwide died of tuberculosis, marking the first time in more than a decade annual deaths from TB have been rising, demonstrating the global need for better access to treatment. To address this problem, scientists from UNC College of Medicine, UNC Institute for Global Health and fitness and Infectious Disorders, and the International Center for Advancing Translational Sciences have developed a long-acting injectable formulation of the anti-tuberculosis drug. rifabutin.

Published in the journal Mother Nature Communications, research in animal models has shown the potential for delivering an anti-tuberculosis drug with a injection that lasts at least four months, instead of the current regular treatment requiring consistent adherence to a daily medication regimen.

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

Co-author Miriam Braunstein, PhD, professor of microbiology and immunology at the School of Medicine of UNC and Fellow of the UNC Institute for Global Health and Infectious Diseases, added, “During the COVID- pandemic, we have witnessed more TB deaths due to disruption or reassignment of health care providers, setting us back at least five to eight years in the global fight against TB. We believe that long-acting formulations could be a game-changer, whether for preventive therapy or disease treatment.

Tuberculosis, which is caused by Mycobacterium tuberculosis ( Mtb), affects approximately million people a year, according to the World Health Organization, which also estimates that around a quarter of the world’s population has one year latent tuberculosis infection with potential for reactivation, resulting in symptoms such as weakness, weight loss, fever, cough, chest pain and coughing up blood.

The non-look strict drug regimens can lead to treatment failure and drug resistance. To overcome this, UNC researchers sought to create a drug delivery system that would provide an effective way to improve medication adherence.

The co- first authors Manse Kim, PhD, postdoctoral researcher at UNC-Chapel Hill, and UNC graduate student Claire Johnson, conducted experiments to combine rifabutin with biodegradable polymers and nontoxic solvents that solidify in the body after subcutaneous injection. Researchers have also added a compound to this formula to dramatically increase the amount of rifabutin that can be included.

Using mouse models, researchers observed how the solidified implant slowly eroded over 16 weeks, releasing their drug payload steadily throughout. This long-acting formulation prevented infection in mice exposed to tuberculosis. Furthermore, the single injection cleared the infection from the lungs and other tissues in mice that had been previously infected with tuberculosis. Researchers observed no adverse effects in mice, but if side effects occur, the implant is removable.

This form of long-acting technology has already been approved by the Food and drug administration for other conditions, such as cancers, schizophrenia and opioid addiction.

“We believe this technology could be used in our fight against tuberculosis worldwide,” said Kovarova. “Further research is needed before Section 1 trials in humans, but our study is an important step towards a much-needed long-acting treatment and prevention strategy for tuberculosis.”

J. Victor Garcia, PhD, professor of medicine at UNC University of Medicine, is co-lead author. Other authors are Alan Schmalstig, PhD, Ayano Annis, Sarah Wessel, Brian van Horne, Amanda Schauer, and Angela Wahl, PhD, all at UNC-Chapel Hill, Agata Exner, PhD, at Circumstance Western University, and Jason Stout, MD, at Duke University.

Basic facilities were critical to carrying out this research: UNC’s Central Nanomedicine Characterization Platform, the UNC Animal Histopathology and Laboratory Medicine Core, UNC Microscopy Services Laboratory, and Clinical Pharmacology and Analytical Chemistry Core.

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