Martina Kovarova, PhD, a member of the Institute for Global Health and Infectious Diseases, and associate professor of infectious diseases, has received a grant from the Bill & Melinda Gates Foundation to develop new Tuberculosis treatment options using ISFI (in-situ forming implant) technology. The TB Alliance, the global not-for-profit developer of TB drugs, is collaborating with UNC to provide therapeutic expertise for the long-acting (LA) injectable formulations study and access to clinical stage as well as marketed TB drugs.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), affected an estimated 10.6 million people in 2022, resulting in 1.3 million deaths. An airborne disease that can be spread by coughing or sneezing, TB is a leading cause of infectious disease morbidity and mortality worldwide. The World Health Organization estimates one-quarter of the world population has a latent TB infection, with the potential for reactivation, leading to symptoms such as weakness, weight loss, fever, coughing, chest pain, coughing up blood, and other manifestations, which if untreated, can be fatal. Among the most vulnerable are women, children, and people living with HIV/AIDS.
While TB is a curable disease, current approaches to preventing, diagnosing, and treating are inadequate. The standard treatment for drug-susceptible TB involves strict adherence to a combination of daily drugs for long periods of time, which can be challenging for patients. Meanwhile, drug-resistant strains of TB are also emerging–there are more than 400,000 cases of drug resistant TB each year–creating a growing sense of urgency to control the spread of the disease.
“Long-acting drug formulations could dramatically change TB treatment, requiring only one or two injections instead of daily administration,” said Dr. Kovarova, whose research has shown the potential to successfully deliver a TB drug with one injection that lasts four months. “This would increase treatment compliance and consequently limit the occurrence of drug resistance.”
LA biodegradable in situ forming implant (ISFI) formulations are attractive because their unique properties allow for subcutaneous administration of liquid formulations, that solidify and form an implant at the site of injection.
“Injectable formulations are less invasive and less painful to administer than solid implants, and the biodegradable nature of the polymer matrix eliminates the need for surgical implant removal,” Dr. Kovarova said. “Although this technology was already used in several FDA-approved drugs, our group was able to improve loading capacity, developing an LA formulation of rifabutin that effectively prevented and treated TB infection in animal models.”
The research team includes Miriam Braunstein, PhD, and Gregory Robertson, PhD (Colorado State University), who will help evaluate the efficacy of the newly developed LA formulation in animal models.