New material paves the way for remote-controlled drugs and electronic pills

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Biomedicines are produced by living cells and are used, among other things, to treat cancer and autoimmune diseases. One of the challenges is that the drugs are very expensive to produce, which limits global access. Now researchers at Chalmers have invented a material that uses electrical signals to capture and release biomolecules. This new and effective method could have a major impact on the development of biomedicines and pave the way for the development of electronic pills and drug implants.

The new material is a polymer* surface which, during an electrical impulse, changes state to go from capturing to releasing biomolecules. This has several possible applications, including use as a tool for the efficient separation of a drug from other biomolecules that cells create in the production of biological drugs. The results of the study were recently published in the scientific journal Angewandte Chemie.

Biodrugs are very expensive to produce due to the lack of an efficient separation technique, and new techniques with higher drug yield are needed to reduce production costs and ultimately the cost of patient treatment.

“Our polymer surfaces offer a new way to separate proteins by using electrical signals to control how they are bound to a surface and released from a surface, without affecting the structure of the protein,” says Gustav Ferrand-Drake del Castillo, who publicly defended his doctoral thesis in chemistry at Chalmers and is the lead author of the study.

The conventional separation technique – chromatography – binds the biomolecules tightly to the surface and strong chemicals are needed to release them, resulting in losses and low yield. Many new drugs have proven to be very sensitive to strong chemicals, creating a major production problem for the next generation of biopharmaceuticals. The low chemical consumption translates into an environmental benefit, while the fact that the surfaces of the new material can also be reused over several cycles is a key property. The process can be repeated hundreds of times without affecting the surface.

Functions in biological fluids

The material also works in biological fluids with buffering capacity, i.e. fluids capable of counteracting variations in the pH value. This property is remarkable because it opens the way to the creation of a new technique of implants and electronic “pills” which release the drug in the organism by electronic activation.

“You can imagine a doctor, or a computer program, measuring a patient’s need for a new dose of drug, and a remote-controlled signal activating the release of the drug from the implant in the very tissue or organ where it is necessary,” says Gustav Ferrand-Drake del Castillo.

Local, activated release of drugs is available today in the form of materials that change state when the surrounding chemical environment changes. For example, tablets of pH-sensitive material are produced when you want to control the release of a drug in the gastrointestinal tract, which is an environment with natural variations in pH value. But in most body tissues there are no changes in the pH value or other chemical parameters.

“Being able to control the release and uptake of proteins in the body with minimal surgical procedures and no needle injections is, in our opinion, a unique and useful property. The development of electronic implants is just one many conceivable applications for many years. Research that helps us connect electronics to biology at the molecular level is an important piece of the puzzle in such a direction,” says Gustav Ferrand-Drake del Castillo.

Another advantage of the new method is that it does not require large amounts of energy. The low power consumption is due to the fact that the depth of the polymer at the surface of the electrode is very thin, at the nanometer scale, which means that the surface reacts immediately to small electrochemical signals.

“Electronics in biological environments are often limited by battery size and moving mechanical parts. Activation at the molecular level reduces both power requirements and the need for moving parts,” says Gustav Ferrand-Drake del Castillo.

The breakthrough started as a doctoral thesis

The research behind the technique was carried out during the period when Ferrand-Drake del Castillo was a PhD student in the research team of Professor Chalmers Andreas Dahlin in the Division of Applied Surface Chemistry. The project involved polymer surfaces that change state between neutral and charged depending on the pH value of the surrounding solution. The researchers then managed to create a material that was strong enough to stay on the surface when subjected to repeated electrical signals, yet thin enough to actually change the pH value due to electrochemistry on the surface.

“Soon after, we discovered that we could use the electrical signals to control the binding and release of proteins and biomolecules, and that the electrode material works in biological solutions such as serum and centrifuged blood. We believe and hope that our findings will be of great benefit in the development of new drugs,” says Andreas Dahlin.

Over the past year, results from Chalmers researchers have been passed on to product development, carried out by spin-off company Nyctea Technologies. The company already has customers among leading researchers and pharmaceutical companies.

* Polymers are chemical compounds that consist of very long chains made up of smaller repeating units. Common plastics are a form of polymer.


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