The podcast "The Next Discovery" is a six-episode series created by Observador, a leading Portuguese digital newspaper and radio station, in partnership with Hovione.

From asthma to therapies that may one day reach the brain, we follow Hovione’s journey in respiratory and nasal drug delivery, where every particle is engineered to improve patients’ lives.

What if some of the scientific breakthroughs that could improve the lives of millions of people were happening right now in Portugal? Welcome to The Next Discovery.

Listen to the fifth episode of the podcast here, featuring Eunice Costa, Director of Research and Development Center at Hovione.

[English transcription]

Nelson Ferreira (NF): Welcome to The Next Discovery. This is a partnership between Rádio Observador and Hovione, a six-episode series where we open the doors to science and innovation with global impact. I’m Nelson Ferreira, and today we’ll explore how the respiratory system and the nasal route are being used to deliver medicines throughout the body in fast and innovative ways. Joining us is Eunice Costa, Director at Hovione’s Research and Development Center.

NF: Hello, Eunice, and welcome. Hovione’s history is closely linked to the lung. More than two decades ago, you began developing and manufacturing solutions for inhaled medicines. What are the major diseases whose treatment has advanced significantly with the help of these innovations?

Eunice Costa (EC): Hello, Nelson. Thank you for the invitation. To begin with, respiratory diseases are among the most prevalent conditions and have a tremendous societal impact. We have asthma and chronic obstructive pulmonary disease, or COPD. The technology required to manage these diseases, from molecule design to formulations and delivery devices, is fundamental to making them manageable. While they certainly have a significant impact on patients’ daily lives, these conditions can be effectively controlled, allowing people to live normal lives.

NF: Especially because some of them aren’t curable.

EC: Exactly.

NF: COPD is one example.

EC: That’s right. The medicines available today are primarily aimed at disease management, particularly bronchodilation, keeping the airways open and unobstructed.

NF: Is that what an asthma inhaler does?

EC: Exactly. That’s what the asthma inhaler does, the device everyone recognizes. It’s probably the most iconic example, and one that we often see used incorrectly in movies.

NF: Really? Is it also what we use during a spirometry test?

EC: Spirometry is primarily a diagnostic test that measures lung capacity when disease is already present.

NF: But an inhaled medication is also used during the procedure, right?

EC: Exactly.

NF: Today, Hovione is also proud to offer end-to-end solutions for inhaled and nasal medicines, primarily targeting the lungs, as we’ve been discussing. Does that mean you control the entire process, from molecule synthesis all the way to the final inhaler device?

EC: Yes, exactly. And the journey has been very gradual and organic, so to speak. If I can make a chemistry joke, “organic” fits quite well. But let’s continue. Hovione started with molecule synthesis, which is part of our history. From there, we specialized in controlling what we call particle size, or particle engineering, because these medicines need to be carefully engineered to be delivered effectively to the lungs.

We handle synthesis, though we don’t work in drug discovery itself. We’re not discovering new molecules; rather, we support pharmaceutical companies with synthesis and, in this case, particle engineering, which is critical for inhaled medicines. Next comes combining the active pharmaceutical ingredient with additional components to create a medicine, which is also far from simple. Finally, there’s the inhaler, the medical device people actually see. It’s the engine that generates the aerosol.

In the traditional asthma inhaler, which is the best-known example, aerosol generation is active. A pressurized gas propels the medication. In the types of devices we specialize in, known as passive devices, dry powder aerosols are generated using the patient’s own inhalation effort.

NF: The patient inhales the powder.

EC: Exactly. It’s still a challenge because there needs to be a perfect combination of particle properties, formulation, and device design to create the aerosol and achieve effective deposition in the lungs. We have control over all those aspects.

NF: The lung seems like a particularly challenging organ for drug delivery. What makes it so difficult to ensure the medicine reaches exactly where it’s supposed to go?

EC: Right.

NF: Do you put a GPS on it?

EC: Not exactly. That would be nice. The reality is that the lung has evolved over millions of years to prevent the entry of any foreign particle, whether it’s a pathogen, a virus, or anything else.

NF: That’s its natural behavior.

EC: Exactly, and fortunately for us. The lung is very effective at preventing exposure. It’s often said that if the entire surface of the lungs were spread out, it would be about the size of a tennis court. It’s an enormous surface area. Without defense mechanisms, we would constantly be exposed to harmful particles. Evolution designed the lungs to keep everything out.

When we try to use the lungs as a route of administration to treat patients, we have to find ways to navigate around those defense mechanisms.

NF: Or trick the lungs.

EC: Yes, you could say that. We have to persuade them. The key lies in a magic number: aerosol particle size. Whether it’s a dry powder cloud or a liquid aerosol, the particles need to be between one and five microns in size. We’re talking about particles at least ten times smaller than a human hair.

These are extremely fine powders. Very small particles tend to clump together, absorb moisture, and behave unpredictably. First, you have to reduce particle size, then control those behaviors, and finally use a relatively simple device.

NF: Of course.

EC: A device capable of generating that aerosol.

NF: And one that anyone can use.

EC: Exactly.

NF: I believe Japan crossed paths with Hovione’s story again through the success of Inavir. What is this product, and what impact did it have?

EC: Inavir is a story that goes back several years and is very illustrative of Hovione’s role in this specialized pharmaceutical niche. It’s an area that requires a broad set of competencies.

For context, Inavir is an antiviral medication used to treat influenza. It’s administered directly to the lungs, which are the entry point for the virus. Hovione was involved in developing both the formulation inside the device and the device itself.

The inhaler remains, to this day, the world’s only single-use inhaler. It’s extremely simple because patients using it have the flu. Reusing an inhaler in that situation makes little sense. The goal is to use it once and then discard it.

The challenge was developing an inhaler that was cost-effective and sustainable while being designed for a single administration.

NF: Use it once and throw it away.

EC: Exactly. Since its approval in 2010, it has remained the world’s only single-use inhaler. We can say that millions of people have been treated with a technology developed in Portugal.

NF: That’s also a source of national pride.

EC: Absolutely.

NF: In recent years, the nasal route has generated tremendous scientific interest, particularly because of its potential to reach certain areas of the body, including the brain and central nervous system, more quickly. What makes this route so special? It seems to have no toll booths.

EC: Well, there are a few. We still need to bypass the body’s defense mechanisms.

The nasal route is fascinating because we often associate anything administered through the nose with allergic rhinitis, pollen allergies, or sinus infections.

NF: And allergies in general.

EC: Exactly. Conditions that are very localized. But in reality, the nasal cavity offers extremely rapid absorption. Researchers began exploring it as a gateway for treating conditions not necessarily linked to nasal symptoms.

Initially, this included areas such as pain management, particularly migraines. More recently, it has also been explored as a potential route to the brain itself.

Why? Because our sense of smell originates in the nasal cavity, which contains a network of nerves.

NF: Although what allows us to smell is actually in the brain.

EC: Exactly. This is one of the few non-invasive routes that provides a relatively direct pathway from the nose to the brain through the olfactory and trigeminal nerves. It opens the door to much more patient-friendly approaches for treating disease.

NF: Looking toward the future of healthcare, could nasal delivery eventually replace injections for many therapies? Might we someday say goodbye to needles?

EC: Unfortunately, I don’t think so. So many innovative therapies are being developed, and needles and injections remain the most reliable way to ensure delivery, especially for advanced biologic therapies, where administration efficiency must be close to 100%.

Everything that is prepared must reach the patient. We’re still far from guaranteeing that level of efficiency through the nose or the lungs. Not yet.

NF: Not yet, but there are already significant advantages in certain situations. To bring all these innovations to market, research can’t happen in isolation. Does your team work with scientific and academic partners who accelerate these discoveries?

EC: Absolutely. First and foremost, our partnerships with Portuguese universities have been an essential source of talent and knowledge for the advances we’ve made over the years, particularly in respiratory drug delivery.

The Faculties of Pharmacy in Lisbon and Coimbra, NOVA University, and Instituto Superior Técnico have all been key partners. Not only academic institutions, but also industry partners. Given the complexity of what we do, multiple disciplines need to come together, from mechanical engineering and physiology to biology.

No one achieves major breakthroughs alone. We also collaborate with companies such as Precisepart in Germany in the area of inhaler devices. These partnerships have been absolutely fundamental to our success.

NF: Eunice Costa, scientist at Hovione, thank you for helping us understand how science is transforming lung health and how the nasal route is becoming a gateway for medicines that could improve the lives of millions of people.

This was the fifth episode of The Next Discovery. Next week, we’ll reach the final chapter of this season and explore what almost sounds like science fiction becoming reality. We’ll discover high-dose biologic medicines and learn how cancer treatments may move from hospitals into our homes.

All episodes are available at observador.pt and on major podcast platforms.

Until the next discovery.