Assistant Professor University of Michigan Ann Arbor, Michigan
Mycobacterial lung infections are a major cause of global mortality and are associated with toxic systemic therapies. Clofazimine is an existing off-patent drug that exhibits stand-alone anti-mycobacterial activity and astonishing synergy with other drugs; however, utilization of the existing oral formulation is limited by its slow onset of action and systemic toxicities. By working with the innate physicochemical properties of clofazimine, we have developed an inexpensive, inhaled crystalline powder formulation of clofazimine for direct targeting of infected alveolar macrophages. While oral delivery of clofazimine requires two weeks of treatment for bactericidal effect, statistically significant bactericidal activity was achieved in a tuberculosis mouse model after only a single dose of clofazimine particles by the pulmonary route and retention of the drug in the lung tissue was enhanced by the presence of bacterial infection. Further development is underway to apply these beneficial properties of clofazimine to the inhaled delivery of other antibiotics.
Learning Objectives:
Upon completion, participants will be able to understand how the physicochemical properties of clofazimine make it suitable for inhaled macrophage targeted delivery.
Upon completion, participants will be able to describe the potential impacts of phagocyte clearance on the pharmacokinetics of inhaled crystalline clofazimine.
Upon completion, participants will be able to describe how clofazimine can enhance the pharmacological activity and aerosol performance of other inhaled antibiotics.
