For respiratory diseases, from asthma to COVID-19, inhaled treatments can quickly deliver a drug to the desired target, the lungs. Global health depends on such treatments. As Kristen Popowski, a PhD candidate in comparative biomedical sciences at the North Carolina State University’s College of Veterinary Medicine in Raleigh, and her colleagues wrote: “Respiratory diseases are among the leading causes of morbidity and mortality worldwide, with coronavirus disease 2019 (COVID-19) remaining prevalent in the ongoing pandemic.”

Kristen Popowski [North Carolina State University]
Although lipid nanoparticles offer one delivery vehicle for such treatments, nature creates an obstacle. “The lung has natural defense mechanisms against inhaled particulates, and traditional lipid-nanoparticle vaccines present challenges in cytotoxicity and respiratory clearance,” says Popowski. “A nanoparticle formulation that can withstand these defense mechanisms remains a critical challenge.” So, Popowski and her colleagues explored an alternative approach.

“Instead of disguising vaccines in synthetic lipid nanoparticles, we utilize cell-secreted nanoparticles called exosomes as our drug delivery vehicles to the lung,” Popowski explains. “Our exosomes are secreted from native lung cells and are recognizable by the lung.”

Consequently, she says, “We can minimize pulmonary toxicity and clearance to better deliver and retain vaccines.” In addition, the exosome-based treatments developed by Popowski and her colleagues can be formulated as a dry powder that requires no refrigeration and can have a shelf life of 28 days.

Despite the incentives to take an exosome-based approach to inhaled treatments for respiratory diseases, turning that into a part of bioprocessing requires more research.

“Although commercial manufacturing of exosomes has recently shown extensive improvement, optimization of mRNA loading into exosomes remains a challenge,” Popowski says. “Endogenous mRNA expression through exosome engineering would likely be necessary for large-scale production.”