An ion pump could circumvent the challenges of delivering drugs beyond the blood-brain barrier, an advance that could improve the treatment of malignant brain tumours.
This is the claim of researchers at Linköping University, Sweden, and the Medical University of Graz, Austria, who have shown in cells in culture that an ion pump can deliver drugs more accurately. The scientists used cells from glioblastoma, a common and aggressive type of cancer that occurs in the brain and their results have been published in Advanced Materials Technologies.
“This is the first time an ion pump has been tested as a possible method to treat malignant brain tumours. We used cancer cells in the lab, and the results are extremely promising. However, it will probably take five to ten years before we see this new technology used in treatments for brain tumours”, said Daniel Simon, associate professor at the Laboratory of Organic Electronics at the Department of Science and Technology at Linköping University.
Surgical removal of brain tumours often leaves small parts of the tumour behind, which can require chemotherapy to stop the cancer recurring.
In order to reach the brain, chemotherapy drugs must first spread through the circulatory system and then pass through the blood-brain barrier. The walls of the small blood vessels in the brain are much less permeable than blood vessels in the rest of the body and can prevent many substances in the blood entering the brain.
The scientists have now developed a method in which an implanted ion pump can be used to get around the blood-brain barrier and supply gemcitabine – an effective chemotherapy agent that cannot normally pass the blood-brain barrier – directly into the brain with high precision. Gemcitabine is currently used to treat cancers in the pancreas, bladder and breast, where it disrupts cell division in rapidly growing tumours. Gemcitabine does not affect brain cells because they do not normally undergo cell division.
“The traditional glioblastoma treatment currently used in the clinics harms both cancer and neuronal cells to the same extent,” said Linda Waldherr, postdoctoral fellow at the Medical University of Graz. “However, with the gemcitabine ion pump, we tackle only the cancerous cells, while neurons stay healthy. In addition, our experiments on cultured glioblastoma cells show that more cancer cells are killed when we use the ion pump than when we use manual treatment.”
When the ion pump is to transport gemcitabine from an electrolyte reservoir into cells or a tumour, a low current is used to ‘pump’ the positively charged drug through an ion transport channel.
The low current and voltage mean that eventual therapeutic technology will not require large power supplies or batteries to operate. A low current also avoids activating and transmitting unintended nerve signals in brain cells.
“The pressure inside the brain is extremely sensitive and using an ion pump to transport the drug instead of a fluid-driven device means that the pressure is not affected,” added Rainer Schindl, associate professor at the Medical University of Graz. “Also, the dosage is controlled by electrical charging, which makes the supply of the chemotherapy agent extremely precise. The next step will be to use the ion pump to evaluate different chemotherapy agents that have previously given adverse effects that are too serious or that are unable to pass the blood-brain barrier.”