Mucus coats our airways' internal surfaces. The viscous gel humidifies the lungs and prevents viruses and other small particles like diesel soot from entering the body unchecked. Previously unclear was the extent to which such nanoparticles are able to move through the lungs' mucus. Here, the research evidence was contradictory. Scientists could not explain why, in inhaled medication development, drug nanoparticles often simply got stuck in the mucus never making it to their target destination inside the lung cells.
Now, as part of a German Research Foundation (DFG)-funded study, pharmacists and physicists were finally able to shed light on this dilemma. Scientists from the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the HZI, together with researchers from the Saarland University, the Universit- Paris-Diderot, and Fresenius Medical Care Germany collaborated on the study. "The mucus inside the lungs is a very special kind of gel. Its structure is very different from other gels," explains Claus-Michael Lehr, Professor for Biopharmacy and Pharmaceutical Technology at the Saarland University and head of the "Drug Delivery" Department at HIPS. "Normal" gels have a microstructure that resembles a delicate spiderweb made from thin, very fine threads that enclose small pores. When viewed under the microscope, lung mucus, by comparison, looks more like a sponge, with rigid, thick gel rods separating large pores filled with liquid gel. "These scaffold proteins are called mucins," explains Professor Lehr. The researchers have now shown that nanoparticles become stuck at these structures as though they were bars of a cage. The explanation for why many investigations found nanoparticles in the mucus to be highly mobile is because the research was done on a nanometer scale. Inside the pores, the particles can move around completely unobstructed and only when they try to move past individual pores are they prevented from doing so by the "bars."
"Our results are helping us to better understand the etiology of infectious diseases of the airways and how to treat them more effectively. In particular, they represent an important basis for the continued development of new inhaled medications," explains Professor Lehr. The newly gained insights show that it is important to consider how drugs overcome the mucus gel scaffold. Mucolytic techniques can be used where, essentially, the rods are melted such that they dissolve before the nanoparticle and, once the particle has passed, they fuse again.