Novel Characterisation of Nanoparticles as Lung Surfactant Protein Substitutes towards New Treatments for Infant Respiratory Distress Syndrome

Infant respiratory distress syndrome (IRDS) is a tragic health condition when premature babies cannot breathe by themselves at birth. The cause of the condition is that soap-like molecules that coat the surface of our lungs and allow us to breathe, called lung surfactant, have not had enough time to mature during pregnancy. The purpose of lung surfactant is to reduce the surface tension of the fluid in our lungs, which in turn reduces the energy we need to expend when we breathe. Without enough of the surfactant produced during pregnancy, babies who suffer from IRDS do not even have the strength they need to take their first breath.

Lung surfactant is a complex mixture of biological molecules, and the key component missing in premature babies is a protein. It has a special function that allows the rest of the surfactant coating the lung fluid to gather in small pockets as the surface area is small when we breathe out, enabling them to reorganise very quickly and keep the fluid coated as the surface area increases when we breathe in. In the absence of the protein, the surfactant molecules struggle to keep the fluid coated throughout breathing cycles, the surface tension goes up, and the lungs collapse.

Unfortunately, it is too expensive and difficult for drug companies to make this protein, and scientists have not yet managed to design replacement molecules that have the same function. Current medicines are crude extracts from animal lungs with no design efforts having been made to make them well suited for use in humans. These treatments are good in that survival rates are high, but a serious bowel condition can be a severe side effect, and the medicines have such poor shelf life they are not widely available in developing countries. Further efforts are clearly needed to develop new and improved treatments.

This research project builds on two recent discoveries I have made whilst working as a scientist studying the behaviour of biological films on the surface of water. I reflect light off the films, and just like we can use our eyes to distinguish different objects when we see light that has reflected off them, the laser instruments in my lab work in the same way except that the information is about single layers of molecules. The first discovery was that when I squeezed certain films to reduce the surface area, like when we breathe out, I could generate these pockets of material if the films contained certain types of tiny particles called nanoparticles. The second discovery was that when I made films made of lung surfactant itself, I could use my laser reflection techniques to see the depth and diameter of these pockets formed at very low surface tension for the first time.

These breakthroughs have created an exciting opportunity to use reflection techniques to work out the important properties of nanoparticles that can help form the vital pockets of material in lung surfactant. First, the project will consider effects of the size, charge, affinity (oil vs water) and degree of swelling of the nanoparticles in their ability to recreate the performance of healthy lung surfactant in the absence of the protein. Second, the most promising nanoparticles will be dressed up in a cloak of relatively cheap portions of the original protein to see if this could be an even better way to reach optimal performance.

The overarching goal of the project is to establish knowledge on the ability of nanoparticles to help recreate the performance of healthy lungs with a view to the future design of new medicines to treat IRDS. The ambition of developing these new medicines is that they could result in fewer side effects and/or have an improvement in shelf-life, which in turn can lead to improvements in health here in the UK or in survival rates in developing countries. The work will also provide a platform to establish the UK as a scientific and medical leader in the treatment of IRDS on which it is currently missing presence.