Despite tuberculosis (TB) mortality has fallen 47% since 1990, TB remains one of the world's deadliest diseases. Indeed, TB ranks alongside HIV as a leading infectious disease killer. The World Health Organization (WHO) estimated over 10.4 million new cases and 1.8 million deaths, including 0.4 million among people with HIV, by 2015. Over the past decade, drug discovery and development efforts have yielded a few new interesting anti-mycobacterial agents, including the imidazo pyridine amide Q203, the nitroimidazole PA-824, the 1,2-diamine SQ-109, and the benzothiazinone BTZ-043. However, due to high attrition rates, further new compounds are needed. Concurrently, new approaches are also needed to get a faster, more-efficient and less harmful treatment. In the last few decades, there has been a growing interest toward the use of new delivery systems for a more effective treatment of infectious diseases focused on nanotechnology platforms (e.g., polymeric nanoparticles and liposomes) for the targeted delivery to the lungs. The development of new inhalable nanovectors to achieve net drug delivery to the lungs could significantly improve TB treatment by reduction of systemic toxicity and accomplishing higher drug concentration at the main site of infection.
The project proposed here aims at combining new chemical entities, acting by novel mode of action, with inhalable nanovectors for drug-susceptible, MDR and XDR-TB treatment. We expect that the administration of new and more potent anti-TB compounds in nanoparticle-based formulations can improve patient adherence by shortening drug regimen duration as well as reducing frequency and ultimately improving completion rates with the final goal of significant reduction of MDR-TB cases.
