An army of microrobots to deliver drugs to the right place.

"I would fear infinitely if they lost or exchanged their labels, reversing their regions," the 16th-century French thinker Michel de Montaigne stated, referring to the various medicines a patient was taking. It was an interesting concern from a visionary, because centuries later, drugs that don't reach the correct part of the body or that interact with other parts of the body still cause problems. This is one of the causes of drug side effects or their lack of effectiveness.

To avoid this, microrobots have been designed in recent years that can deposit medicine in the exact location it needs. This is a much less fantastical and more rigorous approach than the hallucinatory journey that Isaac Asimov novelized in 1966, based on the screenplay of the film of the same name. An international team led by Salvador Pané and Bradley J. Nelson, from the Swiss Federal Institute of Technology Zurich (ETH), has created a new microrobot platform that has already proven its effectiveness in initial tests in vitro and in vivo. Their study has just been published in the journal Science.

A magnetic navigation system

Research on these tiny robots has been very intensive over the last two decades, but the aspects to be studied are diverse: their movement and how to guide them within the body, and the systems for drug delivery. To address the first point, Pané and Nelson's team has used an electromagnetic navigation system called Navion. It can generate controllable magnetic fields to guide the capsule through the neurovascular system, "a milestone never before achieved in the field of microrobotics," Pané explained to ARA. He added that this allows it to "roll along the vascular walls, move by traction with a gradient, or be guided magnetically—as if the magnetic field were a ship's rudder—taking advantage of the blood flow."

Another requirement concerns the materials to be introduced into the body. The system also incorporates a catheter and the microrobotic capsule. The capsules used consist of a gelatin matrix, which is biodegradable and biocompatible, magnetic nanoparticles for movement and control, and tantalum nanoparticles as an X-ray contrast agent to observe its trajectory. Another of the article's authors, Josep Puigmartí, ICREA researcher and professor of chemistry at the University of Barcelona, ​​explained to ARA that "these are components already approved by the FDA (the US Food and Drug Administration) for other uses, which facilitates their clinical translation." The first tests were carried out with a silicone model that reproduced a patient's vascular system in three dimensions. The model was created using data obtained from magnetic resonance imaging or X-rays. The microrobot, measuring 1.6 millimeters, was inserted into the carotid artery. The device moved through the bloodstream at a speed of 37 cm/s – approximately 1.3 km/h – a normal value for blood in an adult. The test showed that a magnetic field allowed the small device to be guided through various blood vessels.

The second test was performed using the vascular system of a human placenta. in vivo Experiments were conducted on a sheep and, finally, on a pig. Again, it was demonstrated that the microrobot could navigate inside blood vessels and was capable of releasing the drug.

From dissolving a blood clot to treating a tumor

Researchers have found that the platform can deliver different agents, including a thrombolytic agent capable of dissolving a clot. Pané, co-director of ETH's multiscale robotics laboratory, explains that "microrobots are useful in tissues where surgical access is complex or where it's necessary to concentrate the drug to avoid systemic effects: tumors, lesions of the nervous or vascular system, aneurysms..." He adds that they can be used in swarms to perform chemoembolizations, that is, to deprive a tumor of blood supply while simultaneously releasing an antitumor agent. The priority for collaborations with clinical and medical researchers will be high-prevalence, poor-prognosis conditions. In each case, the number of procedures may vary: a stroke may require only one microrobotic capsule, while a tumor may need more. But it's also worth considering that concentrating the drug in the specific tissue significantly reduces the dose. "If progress in older animals continues to be positive and the regulatory process is smooth," explains Pané, "the first human trials could be feasible in 5 to 10 years." In cases of high medical need, a horizon of about 4 or 5 years is plausible.

If he could see it, Montaigne would be more at ease: each drug would go in its place, without losing or changing labels and without acting in the wrong place.