A drug-free nasal spray could become a future weapon to prevent a broad spectrum of respiratory infections caused by various pathogens: common cold, seasonal flu and Covid viruses, but also bacteria that cause pneumonia. Preclinical studies – also conducted on a 3D-printed copy of the human nose – are promising according to the researchers who developed it, experts from Brigham and Women’s Hospital (USA), and suggest that the broad-spectrum nasal spray is long-lasting, safe and, if validated in humans, could play a key role in reducing respiratory diseases and safeguarding public health from new threats, the authors emphasize. The results are published in the journal ‘Advanced Materials’.
“The COVID pandemic has shown us what respiratory pathogens can do to humanity in a very short period of time. This threat has not gone away,” says senior coauthor Jeffrey Karp. “Not only do we have seasonal influenza to deal with, but now we also have COVID.” These infections, scientists say, cause thousands of deaths and hundreds of thousands of cases of severe illness each year. Even mild infections cause discomfort, with the burden of missed work or school. Vaccines and masks can help against these pathogens, but they are not perfect tools. “We need new, additional ways to protect ourselves and reduce transmission,” Karp says.
Most viruses enter our bodies through the nose. An infected person expels tiny droplets of fluid that contain the pathogen. Healthy people around them breathe in these droplets, which stick to the inside of their nose and infect the cells lining their nasal passages. The pathogen replicates and can be released back into the air when a sick person, whether they know it or not, sneezes, coughs, laughs, sings, or even just breathes. The spray, called PCANS (Pathogen Capture and Neutralizing Spray), “forms a gelatinous matrix that traps respiratory droplets, immobilizes the germs, and effectively neutralizes them, preventing infection,” explains co-senior author Nitin Joshi, an associate professor of anesthesiology at Brigham and Women’s Hospital. This spray, he continues, “was developed using ingredients from the FDA’s inactive ingredient database,” the US regulatory body, “that have been previously used in approved nasal sprays. We have thus developed a drug-free formulation using these compounds to block germs in three ways.”
The researchers conducted detailed experiments in the lab; they did not directly study Pcans in humans. After developing the formulation, they evaluated its ability to capture respiratory droplets on a 3D-printed human nose replica, showing that when sprayed into the nasal cavity replica, the spray captured twice as many droplets as mucus alone.
“Pcans forms a gel, increasing its mechanical resistance by 100-fold and forming a solid barrier,” says lead author John Joseph, a former postdoctoral fellow at Brigham and Women’s Hospital. In preclinical tests, the spray “blocked and neutralized nearly 100% of all the viruses and bacteria we tested, including influenza, SARS-CoV-2, respiratory syncytial virus RSV, adenovirus, Klebsiella pneumoniae, and more.” Experiments in mice showed that a single dose of Pcans nasal spray could effectively block infection with an influenza virus (Pr8). “The levels of this virus in the lungs were reduced by more than 99.99%, and inflammatory cells and cytokines in the lungs of treated animals were normal.
“The formulation’s ability to inactivate a broad spectrum of pathogens, including the deadly PR8 influenza virus, demonstrates its high efficacy,” says co-senior author Yohannes Tesfaigzi, AstraZeneca Professor of Medicine in Respiratory and Inflammatory Diseases at Brigham and Women’s Hospital. “In a rigorous study in mouse models, prophylactic spray treatment demonstrated exceptional efficacy, with treated mice showing complete protection, while the untreated group showed no such benefit.” Human studies are lacking, but the work provides a foundation for future research to explore the full potential of Pcans in a broader context, say the scientists, who are also exploring another possible function: whether Pcans can block allergens, potentially opening up a new avenue for allergy relief.
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