Nose to nose with the future of drug delivery

Nasal drug delivery is rapidly becoming an attractive option for emergency medicines and vaccines, and promises easier administration that can be carried out by anyone. The scientific rationale is simple: drugs absorbed through the nasal mucosa bypass the gastrointestinal tract and liver, enabling faster and more efficient uptake. 

“Nasal delivery is one of the big focus areas in drug delivery right now,” says Nikolaj Sørensen, CEO of Orexo, an Uppsala-based drug delivery formulation company. 

Nasal delivery allows for a higher drug load and higher and faster bioavailability, making it both quicker and more precise than other delivery methods, which is crucial especially in emergency situations. In the case of Orexo, three of the four candidates in its pipeline are emergency medications for opioid overdose.

85% of all severe diseases come through the mucosa

Another advantage is the ability to stop infections at the point where many pathogens enter the body – through the nose. This is central to why nasal vaccines may outperform injections, for example against respiratory diseases.

For decades, intranasal vaccination has been considered a “holy grail” because the nasal mucosa is both the entry point for most pathogens and a difficult environment for traditional vaccine technologies.

Maria Alriksson, CEO of Abera Bioscience, another company in Uppsala, which develops nasal vaccines – distinguishes between mucosal immunity, which acts directly in the nasal passages, and systemic immunity, which activates only after a pathogen enters the bloodstream. 

“With mucosal immunity, the immune system reacts already at that physical place,” she explains, without the body having to wait for the virus to enter the blood stream before an immune response is activated.

For decades, intranasal vaccination has been considered a “holy grail” because the nasal mucosa is both the entry point for most pathogens and a difficult environment for traditional vaccine technologies, according to Alriksson.

“If you eliminate the virus in the mucosa, you don’t spread it when you sneeze or cough. You can stop transmission, which could make a huge difference in a pandemic,” she says, and adds that 85% of all severe diseases come through the mucosa.

Given that the nose is designed to flush out irritants rather than absorb them in the mucus, it’s proven difficult to develop a technology that can elicit a strong immune response. Abera’s platform is looking to overcome this by generating strong mucosal and systemic immunity simultaneously. The company develops its own vaccine candidates using a vesicle-based platform that can be decorated with different antigens “in a plug-and-play manner,” as Alriksson puts it.

The same vesicle is used across all their candidates, enabling rapid development of vaccines for influenza, pneumococcal disease, and other pathogens.

Powder vs. liquid nose sprays

While Abera’s candidates – four of which are in pre-clinical stage and another three in the discovery phase – are all liquid formulations, their platform also works for powder formulations, and nasal drugs in powder form offers additional benefits. 

Orexo, on the other hand, has developed a powder-based technology called AmorphOX. The technology has shown good results in chemical degradation over time for many different modalities, including small molecules, peptides, and biologics.

“We are using a powder so we can achieve higher stability and a longer shelf life, and less sensitivity to temperature variations,” Orexo’s Sørensen says. “We have seen that our powder technology AmorphOX delivers very strongly on stability. Vaccines or proteins and peptides – that otherwise are very sensitive – can be kept stable in room temperature using our powder technology.”

When it comes to vaccines, potential targets are air-borne viruses, respiratory diseases, and seasonal flus, Sørensen explains. Together, Abera and Orexo have already demonstrated a powder-based influenza vaccine in a proof-of-concept study. 

The most serious infections definitely emerge in areas of the world where you don’t have access to healthcare infrastructure, and where the temperatures are often high.

Powder formulations could reduce device costs, simplify logistics, and eliminate cold chain requirements. The stability and long shelf life of the powder technology makes it a versatile alternative to traditional vaccines, particularly in under-served regions of the world.

“The most serious infections definitely emerge in areas of the world where you don’t have access to healthcare infrastructure, and where the temperatures are often high. Access to nurses who can travel around with a cooling bag that keeps the vaccines frozen is very limited. The opportunity to give vaccines nasally in those regions is very promising,” Sørensen says.

“We are using a powder so we can achieve higher stability and a longer shelf life, and less sensitivity to temperature variations,” says Nikolaj Sørensen, CEO, Orexo.

Regulatory challenges on the road ahead

Despite the promise, nasal vaccines are still few and far between. As a nascent drug delivery method they face hurdles, and drug developers in the area need to find new regulatory pathways and regulatory acceptance. 

Despite this, Alriksson is confident about the long-term trajectory. Besides the obvious medical advantages, a non-injectable vaccine alternative may be easier for the general population to accept, she reflects. 

“No one wants to give their children injections if there’s an easier way,” she says, and continues: “Then you have widespread vaccine hesitancy where injections are troublesome in the sense that people are afraid of needles, so you could gain larger acceptance.”

With a nasal spray, you can increase the number of people vaccinated, compared to an injection. We truly believe nasal vaccines can revolutionize the vaccine industry.

FluMist, a live attenuated influenza vaccine, is the first of its kind to be approved in the US and can be self-administered, demonstrating another benefit of nasal drug delivery – it’s easier to use and can be done by the patient themselves or a caregiver.

“With nasal drug delivery we get easier administration, especially when looking at mass administration in the case of a pandemic, for example. This means that the burden of delivery and administration is removed from the healthcare system. So, with a nasal spray, you can increase the number of people vaccinated, compared to an injection,” Alriksson says. “We truly believe nasal vaccines can revolutionize the vaccine industry.”