Preclinical studies suggest that a drug-free nasal spray could ward off respiratory infections

A new study details how a nasal spray developed by researchers at Brigham and Women's Hospital can protect against viral and bacterial respiratory infections. Based on their preclinical studies, the researchers say the broad-spectrum nasal spray is long-lasting and safe and, if proven effective in humans, could play a key role in reducing respiratory disease and protecting public health from emerging threats.

Their results were 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. That threat has not gone away,” said co-senior author Jeffrey Karp, Ph.D., distinguished chair of anesthesiology at Brigham and Women's Hospital. “We're not only dealing with seasonal flu, but now we're dealing with COVID.”

Flu and COVID-19 infections cause thousands of deaths and hundreds of thousands of cases of severe illness each year. Milder infections cause significant discomfort, leading to missed work or school.

Vaccines against these viruses can be helpful, but they are not perfect. Vaccinated people still get infected and spread the infection to others. Masks are also helpful, but they are not perfect either – they can leak and many people wear them incorrectly or choose not to wear them at all.

“We need new, additional ways to protect ourselves and contain the transmission of the disease,” Karp said.

Most viruses enter our bodies through our noses. When we contract an airborne infection like flu or COVID, we breathe out tiny droplets of fluid containing the pathogen. Healthy people around us breathe in these pathogen-containing droplets, which lodge in their noses and infect the cells that line the nasal passages.

The pathogen multiplies and can be released back into the air when a sick person – whether consciously or unconsciously – sneezes, coughs, laughs, sings or even simply breathes.

The new study details the research team's efforts to develop a nasal spray to protect against airborne respiratory diseases.

“The spray, called Pathogen Capture and Neutralizing Spray (PCANS) in the study, was developed using ingredients from the FDA's Inactive Ingredient Database (IID) that were previously used in approved nasal sprays or from the FDA's Generally Recognized as Safe (GRAS) list,” said co-senior author Nitin Joshi, Ph.D., assistant professor of anesthesiology at Brigham and Women's Hospital.

“We have developed a drug-free formulation with these compounds to block germs in three ways – PCANS forms a gel-like matrix that captures respiratory droplets, immobilizes the germs and effectively neutralizes them, thus preventing infection.”

The researchers conducted the experiments described in the study under laboratory conditions. They did not directly study PCANS in people. The researchers developed the formulation and studied its ability to capture respiratory droplets in a 3D-printed replica of a human nose. They showed that when sprayed into the replica of the nasal cavity, PCANS captured twice as many droplets as mucus alone.

“PCANS forms a gel that increases its mechanical strength 100-fold, creating a solid barrier,” said lead author Dr. John Joseph, a former postdoctoral fellow at Brigham and Women's Hospital. “It blocked and neutralized nearly 100% of all viruses and bacteria we tested, including influenza, SARS-CoV-2, RSV, adenovirus, K pneumonia, and more.”

Experiments in mice showed that a single dose of PCANS nasal spray was effective in blocking infection with influenza virus (PR8) at a dose 25 times the lethal dose. The virus concentration in the lungs was reduced by >99.99%, and inflammatory cells and cytokines in the lungs of PCANS-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,” said co-senior author Yohannes Tesfaigzi, Ph.D., AstraZeneca Professor of Medicine in the Division of Respiratory and Inflammatory Diseases at Brigham and Women's Hospital.

“In a thorough study of mouse models, prophylactic treatment with PCANS demonstrated exceptional efficacy, with treated mice showing complete protection while the untreated group showed no such benefit.”

Although the study is limited by, among other things, the lack of human studies on PCANS, it provides a solid foundation for future research to explore the full potential of PCANS in a broader context. The researchers are investigating whether PCANS can also block allergens, opening up a potential new approach to allergy relief.