UNC Chapel Hill Research on Long Release Drugs for Fighting Tuberculosis

Scientists at UNC and the International Center for the Advancement of Translational Science have developed a long-acting injectable formulation of the anti-tuberculosis drug rifabutin (RFB). Making use of already FDA-approved technology, these scientists can make use of leaps in materials science and medication to create a more reliable treatment for a disease that could be latent in 23% of the world’s population. 

As opposed to the current course of antibiotics used to treat tuberculosis (TB), this technology will allow doctors to inject patients with a serum that will carry RFB in a suspension of liquid polymer (PGLA). This injection will solidify in the patient and create an implant that will slowly release medication over the course of months, essentially making the whole treatment manage itself after the initial administration. 

Tuberculosis Being a Problem

Caused by Mycobacterium tuberculosis (Mtb) as of 2018 resides in the lungs, TB has already become the leading infectious disease killer in the world, claiming 1.5 million lives each year.

Treating this disease is a difficult proposition as not only does it normally appear in places with underdeveloped health systems but can take anywhere from 4 to 9 months to treat. This large treatment window leaves opportunities for patients to skip days of treatment and create antibiotic resistance in the Mtb inadvertently.   

Those unfortunate enough to be afflicted with tuberculosis are often struck with symptoms such as weakness, weight loss, fever, coughing, chest pain, and coughing up blood. These symptoms all reduce the quality of life and the ability of adults to function in society.  These impediments are the cause of the fact that The Lancet estimates that the world is on track to resulting in a loss of $17.5 trillion from a lost economic activity from 2020 to 2050. 

To overcome this, UNC researchers sought to create a therapeutic delivery system that would provide an effective way to improve adherence to medications. 

Long Release Implants and Long Term Benefits

The long-acting technology that was approved by the FDA for cancers, schizophrenia, and opioid dependency works by containing anti-TB drugs (rifampin RIF, rifapentine RFP, and rifabutin RFB) inside of PGLA. These drugs are both bactericidal and inhibit DNA-dependent RNA synthesis in prokaryotes. RFB’s high hydrophobicity improves its uptake in the body.

This allows a removable implant to slowly release medication over the course of months and eventually dissolve possible. In a country where access to medical treatment, and thus refilling prescriptions, is difficult, a single doctor’s visit that gives a patient all the resources needed to treat an illness with no need for upkeep on their part has massive advantages over medication that needs to be resupplied and taken regularly. 

In the mouse model, the solidified implant slowly eroded over the course of 16 weeks, releasing its drug payload in a sustained fashion throughout. This long-acting formulation prevented infection in mice exposed to TB and cleared infection from lungs and other tissues in mice that had been previously infected with TB with no adverse effects.  

The benefits of the research conducted by Dr. Manse Kim and Claire Johnson of UNC will undoubtedly contribute to the reduction of lethality for the world’s deadliest infectious disease. Being able to deliver a treatment that requires a single injection is able to dissolve on its own and further validates an increasingly relevant technology in modern medicine.

Author

Eduardo Longoria