Scientists 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 developed a long-acting injectable formulation of the anti-TB drug rifabutin.

Figure 1: A long-acting injectable formulation of the anti-TB drug rifabutin.

Figure 1 shows thatresearch in animal models showed the potential of delivering a TB drug with one injection that lasts at least four months, in lieu of the current standard treatment requiring constant adherence to a daily drug regimen. [1]

"We think our approach could dramatically change TB treatment," said Martina Kovarova. Tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), affects an estimated 10 million people a year, according to the World Health Organization, which also estimates that about 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, and coughing up blood.

UNC researchers sought to create a therapeutic delivery system that would provide an effective way to improve adherence to medications. Researchers led experiments to combine rifabutin with biodegradable polymers and non-toxic solvents that solidify in the body after subcutaneous injection. The researchers also added a compound to this formula to significantly increase the amount of rifabutin that could be included. [2]

The new delivery system also includes amphiphilic compounds that are attracted to both water (hydrophilic) and lipids (lipophilic). This allows the injection of higher loads of rifabutin in a single injection.

In mice, the injectable implant erodes over the course of 16 weeks, releasing its payload in a sustained fashion throughout. The sustained release of the drug is facilitated by the organized microstructure of the solidified implant that can be regulated by changing the composition of the delivery system.

In mice exposed to Mycobacterium tuberculosis, the new long-acting delivery system prevented active infection, and in mice with active tuberculosis infections, the single injection cleared the infection from lungs and other tissues. None of the mice showed any adverse effects. However, in the event of any side effects, the subcutaneous implant can be removed readily.

“We think this technology could be leveraged in our battle against tuberculosis worldwide,” said Kovarova. The team is currently conducting additional preclinical research on larger animals before the long-acting rifabutin formulation can be tested in humans in Phase I clinical trials. [3]

References:

1. https://www.technologynetworks.com/tn/news/new-long-acting-injectable-drug-delivery-system-for-tuberculosis-364532
2. https://www.sciencedaily.com/releases/2022/08/220808162118.htm
3. https://www.genengnews.com/topics/translational-medicine/infectious-diseases/durability-of-tuberculosis-drug-increased-through-new-formulation/

Cite this article:

Sri Vasagi K (2022), A Long Acting Injectable for TB Drug Rifabutin, AnaTechMaz, pp.87