Functional polymers open up new possibilities in personalized medicine. An interdisciplinary team from Stuttgart is working on new classes of materials for this purpose, combining know-how from mechanics and chemistry.
Band-aids that deliver hormones or painkillers are already common in everyday medical practice. When applied to the skin, they serve as a reservoir for the active ingredient, which is gradually absorbed by the body. This absorption of active ingredients via the skin is expected to become increasingly important for the treatment of diseases and wounds. It would be possible to provide even more targeted treatments and eventually further personalize medicine through the use of smarter band-aids, which would make it easier to deal with the specific needs of individual patients. There are many approaches that could bring us closer to this goal, one of which involves functional polymers, which is where Prof. Sabine Ludwigs and Prof. Holger Steeb of the University of Stuttgart come in. Ludwigs holds the Chair of Structure & Properties of Polymeric Materials at the Institute of Polymer Chemistry, while Steeb is Professor of Continuum Mechanics and Director of the Institute of Applied Mechanics (Civil Engineering). “We are currently developing a new class of polymer materials that will have important properties for future applications in personalized medicine,” says Ludwigs. “What makes our approach so effective is that our research combines our expertise in both mechanics and chemistry.”
Bio-compatible polymers for pharmaceutical applications
At first glance, it may seem surprising that polymers will play any significant role at all in the medicine of tomorrow; after all, in our everyday lives, polymers are primarily used in the form of plastics. Yet just as some polymers are used in Plexiglas or car tires, others are used in such things as the casings of enteric-coated capsules. Although they differ greatly depending on the intended use, the one thing that all polymers have in common is that they are huge molecules consisting of a large number of repeating atomic groups. These long polymer chains often form intertwined structures, not unlike a heaped plate of spaghetti, which can be cross-linked through the use of sophisticated chemistry. Ludwigs and Steeb's teams are interested in so-called biocompatible functionalized polymers, which is to say that their chemical and physical properties are not harmful to living organisms or, as Ludwigs puts it more precisely: “What we're trying to identify are biocompatible polymers that are of interest to the pharmaceutical industry.”
It is possible to store medically active substances in polymer networks, which can then be gradually released into the body in a controlled manner, always in the precise quantity that the body needs. These University of Stuttgart teams are involved in a research collaboration with pharmacists led by Prof. Dominique Lunter and Prof. Stefan Laufer of the Eberhard Karl University of Tübingen. As Ludwigs explains: “The traditional approach in the pharmaceutical industry is to use polymers that are listed as approved polymers in reference works for pharmaceutical drug specifications (pharmacopoeias) and then to experiment with them.” Yet the requirements profile of these polymers is often limited, which is why Ludwigs and Steeb have chosen a different approach.
Regulating the release of stored active ingredients in a targeted manner
First they discuss any interesting properties that suitable polymers might have with their colleagues from the University of Tübingen, whereby "interesting" in this context refers to polymers that change their large-scale structure in response to an external stimulus. This change then enables the escape of the stored active ingredient. Oftentimes, a desirable feature, in such applications, is that the release of the active ingredient can be regulated, i.e., that the structural change of the polymer is reversible depending on the external stimulus.
The respective stimuli,” as Ludwigs explains, “could be pH, humidity, or temperature changes.” If, for example, a certain polymer reacts to moisture, it will be capable of absorbing a large number of water molecules without losing its structural properties. Such changes occur autonomously in the polymer network when a predefined stimulus threshold is reached. “However,”she continues, “it is also possible to manually trigger the change in the polymer network by applying an external stimulus, for example, by applying a weak electrical current,” which would require a suitable polymer to be electrically conductive.
Ludwigs' team first produces promising polymers in the lab, which not only have to exhibit the desired functionalization, but also meet certain elastic requirements, as they are supposed to adhere strongly to the skin in the final pharmaceutical product, even when the patient moves around. Steeb's team is studying whether the newly created polymers are able to do this by characterizing the polymer samples under mechanical tension. “That's how we determine their viscoelastic properties,” Steeb explains. “If, for example, the goal is for a polymer to absorb moisture, we can perform our measurements as the water molecules are being incorporated.” Of course it takes a certain amount of know-how to make the measurements possible in the first place. As Steeb explains, "the polymer samples are often so small or so fragile that they can't simply be clamped in a test setup like a metallic sample. Sometimes, for example, you have to apply the controlled force by rolling up the sample."
Our unique selling point is the close integration of chemistry and engineering.Prof. Holger Steeb
A close collaboration between teams at the Universities of Stuttgart and Tübingen
One potential outcome of the tests may be that the polymer sample does not retain the desired properties long enough, in which case Ludwigs' team will be called upon once again. If, however, the measured properties are promising, Steeb's team models the functional material on a computer to predict the polymer's causal relationships, which in turn the chemistry team can use to further improve it. Of course, more tensile tests then need to be carried out following the revision. “Ultimately,” Steeb explains, “it's about gaining a fundamental understanding of the rheology of the polymer in question.” Rheology reveals the conditions under which a material will deform reversibly, permanently, or not at all. “As soon as we have a polymer at the University of Stuttgart that we are satisfied with,” says Ludwigs, “it’s over to the groups at the University of Tübingen who conduct experiments to measure its charging and discharging behavior.” In some cases, this will be followed by further refinements in the University of Stuttgart's chemistry and mechanics laboratories to further enhance the respective polymer.
Potential applications in personalized tumor therapy
Ludwigs and Steeb have now been collaborating on this project for around four years. Functional polymers are the focus of a comprehensive and intensive field of research around the world. “Our unique selling point is the close integration of chemistry and engineering,” says Steeb. And this level of integration has recently become even tighter since the inter-faculty Functional Soft Materials Lab began operations at the start of the year. “This has brought our teams even closer together in their day-to-day work,” says Ludwigs. The laboratory is located at the Stuttgart Center for Simulation Science (SC SimTech), where Steeb is a member of the research management team. The collaboration between Ludwigs and Steeb does not end with functional polymers as a drug delivery mechanism. In the future, as Steeb explains, functional polymers will also be in demand for 3D printing applications for personalized tumor therapies. “Among other things, 3D printing depends on the rheology of the polymers for optimal functionality.”
Editor: Michael Vogel