Credit: Draper Laboratory

The inner ear is called the 'bony labyrinth'—and for good reason. This essential part of our hearing organ consists of a maze of skeletal cavities, including the snail-shell–shaped cochlea, the target of most agents designed to combat hearing loss. Unfortunately, getting drugs into the cochlea has proven a complex puzzle.

Many compounds in pills don't cross the blood-cochlear barrier and come with off-target effects, whereas drugs injected into the space behind the ear drum don't always permeate from the middle ear into the organ's inner recesses. Thus, for deeper drug penetration, some researchers have been working on implantable devices that can directly deliver compounds into the inner cochlear fluid.

The most advanced such model is being developed by Jeffrey Borenstein and his colleagues at the Charles Stark Draper Laboratory in Cambridge, Massachusetts. By combining a microfluidic pump, a drug reservoir, an electronic control system and tiny tubing, Borenstein's team has devised an apparatus that could one day be implanted in the temporal bone just behind the human ear to provide long-term drug delivery in a controlled and timed manner.

“Bringing it to clinical fruition is really what we're aiming to do,” says Borenstein, whose group is working to miniaturize the device, with plans to build a prototype suitable for human clinical trials in 2015. “You can take out quite a bit of that [bone] and not do anything structurally that would cause any problems. That's what the surgeons tell me.”

In collaboration with audiology specialists at the nearby Massachusetts Eye and Ear Infirmary in Boston, Borenstein's team is first testing a prototype on guinea pigs: a contraption about the size of a ring box, with all the components connected to a thin tube surgically implanted in the cochlea. The researchers had tried strapping the device (pictured) to the rodents' backs, but that didn't work. “We started referring to them as 'Little Houdinis' because they literally managed to get out of every jacket or backpack we designed for them,” says Erin Pararas, a Draper scientist. The group eventually found a workaround by fastening the pods surgically to the top of the guinea pigs' heads.

Currently, the researchers are using the device to infuse a chemical called 6,7-dinitroquinoxaline-2,3-dione (DNQX), which temporarily blocks signals between sensory hair cells and nerve fibers leading to the brainstem by blocking glutamate receptors. Thanks to the fact that hair cells close to the entrance of the cochlea pick up higher-frequency sounds than cells further down the length of the coiled tube do, the researchers can track where the drug has traveled using a series of hearing tests. In the future, they plan to switch over to agents that protect or even help regenerate, rather than hinder, the ear's most delicate structure.

“Implantable-type devices are all in the fairly early stages,” says David Borkholder, a biomedical engineer at the Rochester Institute of Technology in upstate New York who is working on an intracochlear drug delivery system in mice. “But I view them as an essential tool that will enable advanced deafness therapy research and development beyond what people do today.” —ED