Drug turns lung cells into slow-release antibiotic depots

A new designer drug that turns lung immune cells into slow-release antibiotic dispensers can clear a lethal pneumonia infection in mice, researchers report. 

In the study, researchers created a compound known as a prodrug, an inactive form of a drug that becomes active only after being metabolized by the body. Prodrugs can be engineered to extend drug half-life, to ease storage and delivery — and to target specific cells or tissues. 

The team’s goal was to create a prodrug that slowly released an antibiotic inside immune cells called alveolar macrophages. Macrophages are large cells that engulf and digest bacteria throughout the body. Alveolar macrophages are found in the lung’s tiny air sacs, the alveoli. 

In earlier research, the researchers had used a similar design to kill bacteria that hide inside macrophages — a survival strategy that lets pathogens evade immune attack and many antibiotics. The new study tested whether the same approach could also kill bacteria in the surrounding lung tissue, said Dr. Shawn Skerrett, professor (Pulmonary, Critical Care and Sleep Medicine).  

“We had seen that the antibiotic stays within cells for an extended period of time, suggesting the macrophages might serve as a reservoir from which the antibiotic would leak out into the surrounding tissue,” Skerrett said. 

The researcher team also included DOM faculty member Dr. T. Eoin West, professor (Pulmonary, Critical Care and Sleep Medicine).