Collaborating researchers from the University of Cambridge in the U.K., the École Nationale Supérieure des Mines in Paris, and the French National Institute of Health and Medical Research (Inserm) recently engineered an electrophoretic drug delivery method to treat neurological disorders via a neural probe implant in rodents.
This novel device prevents seizures by delivering inhibitory neurotransmitters directly to the affected brain region, essentially shutting down the harmful communication between the neurons and ending the seizure, with negligible increase in local pressure. Their findings were published in the journal Science Advances.
Failure of systemic drug treatments to manage neurological disorders, which affects the entire body, has led to developing alternative methods for localized treatment.
While some approaches, such as designer receptors exclusively for designer drugs or convection-enhanced delivery — direct injection of treatment to the brain — are promising, the former is limited by concerns about introducing engineered proteins through viral transplant, whereas the latter may cause increased pressure at the injection site.
To overcome these obstacles, the research team in Cambridge developed a neural probe that pumps ions across a membrane by inducing an electric field. This electrophoretic way of delivery only delivers the drug of interest and not the solvent (a foreign substance needed by other devices to deliver the drug) thereby maintaining the local pressure at a constant state. Furthermore, it does not raise any known safety issues that might arise from using viral transplants.
Christopher Proctor, a postdoctoral researcher in the Department of Engineering and Borysiewicz Biomedical Sciences fellow at the University of Cambridge, focuses on engineering devices and developing materials to enable a seamless connection between electronics and living tissue. In a press release, Proctor explained the significance of this novel approach.
“In addition to be being able to control exactly when and how much drug is delivered, what is special about this approach is that the drugs come out of the device without any solvent,” he said.
Proctor further added that delivery of the drug without solvent allows for intimate interface between the implant and targeted neurons.
“This prevents damage to the surrounding tissue and allows the drugs to interact with the cells immediately outside the device,” he said.
In their experiment, the researchers induced seizure-like events by injecting 4-aminopyridine (4-AP) into the hippocampi of mice. 4-AP is known to prolong the action potential by blocking voltage-gated K+ channels, causing synchronous firing of a large neuron population.
After the induced seizure, the implanted neural probe can stop the seizure-like events by delivering the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into targeted cells.
The research team found several significant findings. First, the response to 4-AP injection was the same regardless of the presence of the implant. Second, GABA delivery after 4-AP injection eliminated abnormal spike rates and pathological events. Third, neither abnormal spikes or seizure-like events were observed when GABA was delivered prior to 4-AP injection.
These results point out that this electronic implant is compatible with the body and interfaces well with living tissue.
George Malliaras, the Prince Philip professor of technology in Cambridge’s Department of Engineering, shared his insight into the implant technology.
“These thin, organic films do minimal damage in the brain, and their electrical properties are well-suited for these types of applications,” Malliaras said in a press release.
Furthermore, the researchers suggested combining this drug delivery method with advanced algorithms that can predict onset of seizures could establish a closed-loop system that prevents seizures before they occur.
Besides using this device in the context of epilepsy, its advantages open new promising avenues to treating other neurological disorders. Future endeavors in the field will likely focus on delivering dopamine for treatment of Parkinson’s disease or chemotherapeutic drugs for treatment of brain tumors.
