An MIT associate professor, Paulina Anikeeva, and James Frank from Oregon Health and Science University developed a microfiber technology used to deliver and activate a drug that can be induced to bind to a receptor in the brain by exposure to light. Frank said that one of the significant barriers in light-controllable drugs for modulating neural circuits in the brain in a living animal had been the lack of hardware to enable the simultaneous delivery of light and drugs to the target area of the brain. The researchers say their work offers an integrated approach for on-demand delivery of light and drugs using a single fiber.
The team developed a device that can deliver a “photoswitchable” drug deep inside the brain. Light-sensitive molecules known as photoswitches can be attached drugs to switch the activity on and off with a flashlight. This type of drug is called photopharmacology, and in the new study was used to control neuronal activity and behavior in mice. One challenge in controlling drug activity with light is that the light and the drug has to be delivered simultaneously to the target cells.
Delivery of both simultaneously is a challenge when the target is deep inside the body. The team used multifunctional fibers that contain a fluidic channel and an optical waveguide comprised of many layers of different materials fused together, offering flexibility and strength. Creating the fibers starts with a macroscale fiber that is heated and pulled using a process called thermal drawing. The process makes the fiber longer and nearly 70 times smaller in diameter.
The method allows the creation of hundreds of meters of miniaturized fiber created from the original template at a micrometer scale to minimize tissue damage. In the study, the team used an implantable fiber bundle of 480 micrometers by 380 micrometers that weighed 0.8 grams. The fiber was small enough for the mouse to easily carry it on its head for weeks.
The drug the team used in the delivery system was a modified photoswitchable analog of capsaicin, a molecule found in hot peppers. That particular molecule binds to the TRPV1 receptor on sensory neurons that controls the sensation of heat. The modification allowed the capsaicin to be activated by a 560 nanometer-wavelength of light that was visible green. That wavelength is not tissue damaging.
The fiber was implanted into the ventral tegmental area of the mouse’s brain, a deep region of the brain rich in dopamine neurons controlling reward-seeking behavior. The team found that mice preferred the chamber where they received the receptor-expressing virus that delivered the capsaicin, the photoswitchable receptor ligand, and the green light that activated the drug indicating the drug and delivery system worked.