Through a new formulation, the duration of the Tuberculosis medication has been increased

Through a new formulation, the duration of the Tuberculosis medication has been increased ...

The worldwide death toll from tuberculosis increased by 1.5 million in 2020 for the first time in over a decade, highlighting the need for improved patient care.

We were witnessing further deaths during the COVID-19 epidemic due to disruption or relocation of health services, which resulted in a return to at least five to eight years in the global fight against tuberculosis, according to Miriam Braunstein, PhD, an UNC professor of microbiology and immunology and a member of the UNC Institute for Global Health and Infectious Diseases.

Braunstein is a member of a team of UNC researchers, Case Western University, and Duke University, who have developed a long-acting injectable formulation of a drug (rifabutin) approved for tuberculosis to treat the problem. We believe long-acting formulations might be a game changer, whether it be for preventative therapy or treatment of disease.

Preclinical studies have shown that a single injection of the medication using an upgraded delivery system can last at least four months. The following information was published in a new paper entitled, A long-acting formulation of rifabutin has been approved by the FDA for the treatment of cancers, schizophrenia, and opioid dependence. This is the first attempt at using the technology in the treatment of tuberculosis.

Martina Kovarova, an associate professor of medicine at UNC, and a senior author of the study, believes that our approach may dramatically alter tuberculosis treatment. This concept would help alleviate the strain burden on low-income individuals around the world, as long as better treatment is needed.

Tuberculosis, which is caused by Mycobacterium tuberculosis, affects around 10 million individuals each year, resulting in weakness, weight loss, fever, chest pain, and coughing up blood. However, the current treatment for tuberculosis requires strict daily injections, posing the danger of an failure of treatment and drug resistance if medications are missed. The new delivery system will improve patient compliance and overcome these issues.

Both Manse Kim, a PhD, a postdoctoral researcher at UNC-Chapel Hill, and Claire Johnson, both senior authors of the study, combined rifabutin with biodegradable polymers and nontoxic, biocompatible solvents in the new delivery system, and injected the formulation subcutaneously in mice of the BALB/c strain.

During the polymer phase change, the solvent dissipates to surrounding tissues, leaving formed implants that are only formed of biodegradable polymers and rifabutin, according to Kovarova.

Amphiphilic compounds attracted to both water (hydrophilic) and lipids (lipophilic) have also been introduced in the new delivery system. This allows the injection of higher amounts of rifabutin in one injection.

The addition of a quite small amount of amphiphilic compounds may significantly increase rifabutin solubility, according to Kovarova. Depending on the concentration of the amphiphilic compound to achieve the maximum rifabutin solubility, amphiphilic compounds and rifabutin interact in the non-toxic organic solvent, like in water.

In mice, the injectable implant collapses in over 16 weeks, releasing its payload in a sustained fashion. The chemical's structure is facilitated by changing the composition of the delivery system.

According to Kovarova, all implants showed similar pore sizes on the surface at early stages. However, with time, high drug load formulation showed that the implant retained a minimal pore size longer than the formulation with moderate drug load due to its higher hydrophobicity.

The new long-acting delivery system prevented active infection in mice exposed to Mycobacterium tuberculosis, and the unique injection cleared the infection from lungs and other tissues. In the event of any side effects, the subcutaneous implant may be removed quickly.

According to Kovarova, this technology would be utilized in our fight against tuberculosis in the world. Preclinical research on larger animals is underway, before the long-acting rifabutin formulation may be tested in humans in Phase I clinical trials.

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