Researchers at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, have developed a new inhalable form of tuberculosis (TB) treatment that could significantly reduce the burden of current therapy.
The new therapy delivers a key TB drug directly to the lungs, raising the possibility of less frequent dosing and fewer systemic side effects.
In preclinical studies, the inhalable version kept higher levels of rifampin in lung tissue for up to a week after a single dose, compared with daily oral administration.
The findings, published in Antimicrobial Agents and Chemotherapy, show that the inhalable formulation uses microscopic nanoparticles to carry rifampin, one of the most important and widely used TB drugs, straight to the site of infection.
TB remains one of the world’s deadliest infectious diseases despite being curable. Treatment typically lasts several months and requires multiple drugs that can cause serious side effects, making it difficult for many patients to complete therapy. This contributes to treatment failure and the emergence of drug-resistant TB.
Although rifampin is highly effective, oral dosing has limitations. It can cause liver toxicity, and only a small fraction of the drug reaches the lungs, where TB bacteria primarily reside.
To address these challenges, the research team designed inhalable nanoparticles that deliver rifampin directly to lung tissue. The particles are engineered to be taken up by macrophages, the immune cells where TB bacteria hide, and to release the drug slowly over time.
Hilliard L. Kutscher, PhD, research assistant professor of medicine and the study’s first author, explained that these particles are specially built to go straight to the lungs and be taken up by lung immune cells called macrophages.
“They are designed to slowly release rifampin, stimulate the immune system to better fight TB, and reduce drug exposure to the rest of the body, lowering side effects,” he added.
Because the inhaled formulation remains in lung tissue longer, it could eventually allow for once-weekly dosing instead of daily pills.
The team tested the approach in two mouse models of TB, including a severe model that closely mimics human lung damage. They compared once-weekly inhaled nanoparticle therapy with daily oral rifampin to evaluate how effectively each reduced Mycobacterium tuberculosis.
Results showed that the inhaled nanoparticle treatment delivered rifampin to the lungs more efficiently and maintained therapeutic drug levels for longer.
The next phase of research will explore combining the nanoparticle system with other standard TB antibiotics, as combination therapy remains the cornerstone of TB treatment.