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They are barely thicker than a human hair—yet they could significantly improve the effectiveness of inhaled medications: carrier particles in dry powder inhalers transport the active ingredient and ensure it can be efficiently inhaled into the lungs. How well this works depends strongly on their shape.

A team led by Professor Regina Scherließ at Kiel University (CAU) has now, for the first time, produced tiny carrier particles with precisely defined geometries and used them to investigate the role of particle shape in the inhalation process—employing a highly precise 3D printing technique.

The researchers discovered that particle shape has a marked impact on the amount of active ingredient that can be inhaled. Of the four designs tested, one variant performed significantly better than the others. The results have been in Communications Materials.

Millions of identical mini-particles

An innovative 3D printing method made it possible to produce millions of precisely shaped particles in series. Two-photon polymerization is a process that operates with nanometer resolution. A laser selectively activates tiny points in the material, which immediately harden. Thanks to a new printing technology recently advanced at the Karlsruhe Institute of Technology (KIT), 49 structures can now be produced simultaneously—a major step toward speeding up this process.

For each of the four designs tested, the team produced more than 2 million identical particles. In addition, they created three variants of one particular shape with different surface roughness levels—from fine to coarse. They then combined the particles with a model drug, as in real inhalation formulations.

"For the drug to be effective, it has to detach from the carrier when inhaled and reach the lungs with the airflow," explains first author Melvin Wostry. "If it sticks, it is simply swallowed and never reaches its target."

The tests showed that the geometry of the carrier particles had a decisive influence on how much of the active ingredient was released during inhalation. "One shape we call 'Pharmacone' was the clear winner. Its star-like geometry features several protruding tips on the surface," says Scherließ.

"The fine particle fraction—meaning the portion of the drug in the respirable range below 5 micrometers—was four times higher with this geometry than with the next-best design."

The researchers assume that the distinctive tips of the Pharmacone design increase collisions and rotations between particles, making it easier for the drug to detach. By contrast, surface roughness had no measurable effect on release.

Perspectives for drug development

For now, these tiny carriers are model particles for basic research—they are not suitable for inhalation. Still, the researchers see great potential for future applications. In the long term, such precisely printed structures could serve as biodegradable drug carriers directly integrated into dry powder inhalers.

"Our results show that modern technologies such as high-resolution 3D printing are opening entirely new avenues in pharmaceutical development," says Scherließ. "We can now deliberately influence the behavior of medications through design—a kind of fine-tuning on the micrometer scale."