A Drug-Free Nasal Spray May Shield Against Respiratory Infections | Harvard Medical School

Nov 06, 2024

4 min read

At a glance:

The drug-free nasal spray shielded mice from deadly form of the influenza virus.

In a 3D replica of the nasal cavity, the gel-like substance enhanced capture of respiratory droplets, preventing them from invading the deeper airways.

If confirmed in further studies and in humans, the approach could offer one more tool to counter an array of respiratory pathogens.

Harvard Medical School scientists at Brigham and Women’s Hospital have designed a drug-free nasal spray that coats the inner lining of the nose to shield against viral and bacterial respiratory infections.

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The gel-like spray formulated without active pharmaceutical ingredients is yet to be tested in humans, but the researchers say it created a protective coating that lasted for up to eight hours in the nasal cavities of mice treated with it. If the spray’s safety and efficacy are confirmed in humans, the research team said the approach could play an important role in reducing respiratory diseases and safeguarding public health against new threats.

The results are published in the journal Advanced Materials.

“The COVID pandemic showed us what respiratory pathogens can do to humanity in a very short time. That threat hasn’t gone away,” said study co-senior author Jeffrey Karp, HMS professor of anaesthesia and distinguished chair in Anesthesiology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham health care system. “Not only do we have the flu to deal with seasonally, but we now have COVID, too.”

Each year, influenza and COVID-19 infections cause thousands of deaths and hundreds of thousands of severe infections, and even milder infections can cause significant discomfort, resulting in missed work and school.

Vaccines offer a first-line protection, but no vaccine is 100-percent effective, and infections can still occur.

The nasal spray may turn out not to be foolproof either — no approach is — but it could augment current preventive measures.

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

The nose is a favored gateway into the body for many viruses and bacteria. Most respiratory infections, such as flu and COVID, occur after someone breathes in tiny droplets of fluid that contain the pathogen. Once inside the nose, the viral or bacterial particles inside the droplets infect the cells that line the nasal cavity. The pathogen replicates and travels further down the respiratory tract of the infected individual, sometimes reaching the lungs, where it can cause bronchitis and pneumonia. The pathogen can also be released back into the air when an infected person, whether they know it or not, sneezes, coughs, laughs, sings, or even just breathes in and out.

Current nasal sprays offer limited protection against respiratory pathogens because they have a single mechanism of protection. They either neutralize pathogens or block their entry into the cells lining the nose, and they perform both tasks with limited efficacy.

“We developed a drug-free formulation to block germs in three ways — the spray forms a gel-like matrix that enhances the capture of respiratory droplets, immobilizes the germs blocking their transport into the nasal lining, and effectively neutralizes them, preventing infection,” said co-senior author Nitin Joshi, HMS assistant professor of anaesthesia at Brigham and Women’s Hospital.

The nasal spray, called Pathogen Capture and Neutralizing Spray (PCANS), was developed with nonpharmaceutical ingredients already used in approved nasal sprays or listed in the FDA’s Generally Recognized as Safe (GRAS) list.

The researchers designed the formulation and studied its ability to capture respiratory droplets in a 3D-printed replica of the human nasal passages. The experiments showed that when administered into the nasal cavity model, the spray captured twice as many droplets as naturally occurring mucus, produced as part of the body’s innate defense system.

“PCANS forms a gel, increasing its mechanical strength by a hundred times, forming a solid barrier,” said study first author John Joseph, a former postdoctoral fellow at Brigham and Women’s Hospital.

In the 3D model of the human nasal passage, the spray blocked and neutralized nearly 100 percent of all viruses and bacteria tested, including influenza, SARS-CoV-2, RSV, adenovirus, and Klebsiella pneumonia, the experiments showed.

Next, the researchers tested the spray’s protective effects against a strain of influenza in mice. The spray was rapidly activated following administration into the nose and lasted up to eight hours. A single dose could effectively block infection from an influenza virus at 25 times the lethal dose of the virus. This means that the spray was capable of warding off infection even when animals were exposed to a heavy load of the virus. Notably, virus levels in the lungs of pretreated animals were reduced by nearly 100 percent, compared with nontreated animals. The levels of various immune and inflammatory cells in the lungs of treated animals also remained normal.

“The formulation’s ability to inactivate a broad spectrum of pathogens, including the deadly PR8 influenza virus, demonstrates its high effectiveness,” said co-senior author Yohannes Tesfaigzi, AstraZeneca Professor of Medicine in the Field of Respiratory and Inflammatory Diseases at Brigham and Women’s Hospital and HMS. “In a rigorous mouse study, prophylactic treatment with PCANS demonstrated exceptional efficacy, with treated mice exhibiting complete protection, while the untreated group showed no such benefit.”

Adapted from a Brigham and Women’s press release.

Additional Brigham and Women’s authors include John Joseph, Helna Mary Baby, Joselyn Rojas Quintero, Yohannes A. Mebratu, Purna Shah, Kabir Swain, Dongtak Lee, Shahdeep Kaur, Xiang-Ling Li, John Mwangi, Olivia Snapper, Eli Agus, Sruthi Ranganathan, Julian Kage, Jingjing Gao, Anthony Yu, and James N. Luo. Authors also include Remya Nair (Harvard Medical School), Devin Kenney, Florian Douam, Eshant Bhatia, and Dongsung Park. Joseph, Baby, and Quintero contributed equally to this work.This study was supported by funding from the Gillian Reny Stepping Strong Center for Trauma Innovation at Brigham and Women’s Hospital, and the Department of Anesthesiology, Perioperative, and Pain Medicine at Brigham and Women’s Hospital.John Joseph, Helna Mary Baby, Yohannes Tesfaigzi, Jeffrey Karp, and Nitin Joshi have one pending patent based on the PCANS formulation described in this manuscript. BWH has licensed the technology to Akita Biosciences, which has now commercialized PCANS as Profi Nasal Spray, a personal care product, and it is readily available to the public. Joshi and Karp are paid consultants, scientific advisory board members, and hold equity in Akita Biosciences, and the company, BWH, Joshi, and Karp may benefit financially if the IP is further validated. Karp has been a paid consultant or equity holder for multiple other biotechnology companies.