Engineered drug carrier offers new hope for treating serious respiratory disease

This is an illustration of mucus and cilia in the lungs.

Researchers at the University of Virginia (UVA) School of Engineering in Charlottesville have engineered a polymer-based device to cure serious respiratory diseases. The device — bottlebrush polyethylene glycol, or PEG-BB — acts as a drug-carrying molecule and can travel past the lung’s natural defenses undetected.

This is a photo of Baiqiang Huang, who is quoted in the story.Baiqiang HuangUsing the lab’s own “micro-human airway” to test the device, engineers discovered it captures the geometric and biological features of human airways. The findings of their study, Bottlebrush Polyethylene Glycol Nanocarriers Translocate across Human Airway Epithelium via Molecular Architecture-Enhanced Endocytosis,” were published in the American Chemical Society journal ACS Nano.

According to Baiqiang Huang, a UVA materials science and engineering PhD candidate, the human lung has layers of protection that capture and spread pathogens/inhaled particles away from the respiratory system to reduce illness.

“Unfortunately, those same barriers also stop medicine from reaching targeted cells, making it hard to treat diseases such as asthma, chronic obstructive pulmonary disease and pulmonary fibrosis,” Huang said in an UVA Engineering news release.

The PEG-BB mimics mucins (a natural glycoprotein that makes up mucus) and glides through the airway in a bottlebrush movement.

“We thought the flexibility and wormlike geometry of the bottlebrush carrier would let it sneak through the tight mesh of mucus and gels surrounding the cilia to be internalized by epithelial cells, where the drugs are needed to work,” Huang said.

Researchers cultured human airway epithelial cells in their device, adding dual-direction, fluorescent PEG-BB molecules into the cells. They used a dye that can penetrate layers of mucus and periciliary layers to mark the epithelium’s boundaries, using a dark room and a special microscope to observe how the bottlebrush molecules moved through the cells.

This is a photo of Liheng Cai, who is quoted in the story.Liheng Cai, PhDThe lab’s next step is to test PEG-BB’s ability to carry drug molecules across a mucus barrier. The team is experimenting with both in vitro and in vivo models in mice.

“We think this innovation not only promises better treatments of lung diseases with reduced side effects, but also opens possibilities for treating conditions affecting mucosal surfaces throughout the body,” said Liheng Cai, PhD, UVA assistant professor of materials science and engineering.            

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