The biopolymers behind a multimodal nasal spray

The makers of a nasal spray launched last year by start-up Akita Biosciences have pulled back the curtain on how their product works (Adv. Mater. 2024, DOI: 10.1002/adma.202406348). The company’s researchers describe how the spray coats the nasal cavity with a protective layer, captures droplets from the air, and neutralizes them—all using ingredients that the US Food and Drug Administration has categorized as inactive or generally recognized as safe (GRAS).

The researchers call the product pathogen capture and neutralizing spray (PCANS); its market name is Profi.

Nitin Joshi and Jeff Karp, coauthors and Harvard Medical School anesthesiology researchers, originally intended to create a nasal spray to help treat multiple sclerosis. Karp says that when the COVID-19 pandemic hit, they reengineered it as a preventive for airborne nasal pathogens more broadly.

“We started to think, maybe there’s a real opportunity here to create a nasal spray that could provide an additional layer that would essentially block entry of the virus at a major point of where the virus is taking hold in our bodies,” Karp says. “So we developed this nasal spray. We also set the boundary conditions to be, we don’t want this to contain any drugs, because it’s going to take 10 years to get to market.”

Karp and Joshi selected several mucoadhesive biopolymers from the FDA’s inactive ingredient and GRAS databases and evaluated them against several requirements, including their ability to be sprayed and their structural integrity in the presence of simulated nasal fluid. Of the polymers, gellan provided the best “broad spectrum physical barrier,” they write in the paper. Next, the researchers screened compounds for their ability to broadly neutralize pathogens by testing them against SARS-CoV-2 and influenza A with carrageenan as a control. They found that pectin, gellan, and benzalkonium chloride showed the best neutralizing activity. Those three polymers form the basis of PCANS, along with phenethyl alcohol for sanitation and shelf life.

The researchers tested their nasal spray in mice they infected with influenza. All the mice that were given PCANS survived, including one that was given a lethal dose of mouse-adapted H1N1. The spray appeared to be safe and effective in the rodents for up to 4 h. Karp and Joshi also compared PCANS to mucus in a 3D model of a human nasal cavity and found that the PCANS coating “significantly increased the capture of large respiratory droplets.”

“The protection against influenza infection in mice is impressive . . . and clearly demonstrates the ability of PCANS to prevent virus infection, and reduce viral load and inflammatory responses in the lung,” Herman Staats, a professor of pathology at Duke University who studies ways to induce immune responses in mucosal surfaces, says in an email. Staats reviewed the paper independently. “More testing would be needed to determine the safety and efficacy of this product in humans.”

Karp and Joshi cofounded Akita Biosciences to launch PCANS as Profi commercially last year. Because the spray contains no active drug ingredients, it doesn’t have to go through human clinical trials before being sold—the same logic that applies to nutritional supplements.

The pair chose this approach intentionally so that they could bring a potential solution to market more quickly. But the lack of human data raises questions about Profi’s real-world safety and efficacy, especially given that some of the chief users of nasal sprays to prevent respiratory infection are medically vulnerable people.

“Without any clinical data, it’s extremely difficult to assess how well this spray works,” says Aaron Glatt, an epidemiologist at Mount Sinai South Nassau who reviewed the paper independently.

Glatt points out the lack of information about potential allergic responses, as well as the potential for interaction with other medications. “We have so many unfortunate scenarios where people have tried things and it didn’t work out,” he says. “I would be very concerned about anybody using this without any evidence in humans.”

Akita’s leaders present Profi as a layer of protection to be used alongside other measures like masks and vaccines, and CEO Alex Revelos has held webinars to educate potential customers and physicians about the product. But the start-up stops short of saying that Profi can prevent COVID-19 infection, as that would be a medical claim the FDA has not evaluated.

Some of Akita’s competitors have landed in hot water with federal agencies by overselling their own nasal sprays as COVID-19 preventives. The FDA has sent warning letters to at least five manufacturers: Salvacion USA, maker of Covixyl Nasal Spray; CofixRx, maker of a nasal spray of the same name; Amcyte Pharma, maker of Nasitrol; Global Life Technologies, maker of Nozin; and Novid Group, maker of Novid Nasal Spray. In 2021, the Federal Trade Commission also sued Xlear, alleging that the company “falsely pitched its saline nasal sprays as an effective way to prevent and treat COVID-19”—a violation of the COVID-19 Consumer Protection Act.

In their paper, Joshi and Karp acknowledge the limitations that come with a lack of human data. They suggest future studies in large animal models, like nonhuman primates, whose noses more closely mimic those of humans. Tarik Massoud, a radiologist at Stanford University who reviewed the paper for C&EN, also suggests “beta testing” in a small cohort of patients.

There are strong reasons to pursue nasal sprays as pre-exposure prophylacticsagainst respiratory infections, Massoud says in an email. “A nasal spray that has multiple modes of action, as the PCANS described in this report (with capture, barrier-formation, and neutralization properties), would seem a conceptually better idea than other sprays possessing a single mechanism of action.”