Our clinical collaborators at MEEI have tested a version of our drug-delivery system on guinea pigs. Many compounds with known effects on hearing exist, and we are using these formulas to evaluate our system.
So far, the results have been very encouraging: We were able to circulate a liquid drug well into the depths of the cochlea, and we found that the fluid manipulations didn't harm the guinea pigs' ears. Even more compelling were our experiments in which we deliberately modulated their hearing. We started by infusing about 1/1000th of a milliliter of a test compound into a guinea pig's ear through a catheter that had been surgically implanted. The catheter's inner diameter was 100 micrometers, or about the width of a human hair, and it was connected to a pump and control system worn by the guinea pig. We then withdrew roughly the same quantity of fluid, now mixed with the perilymph, and repeated the infuse-withdraw cycle for several hours.
One of the beautiful things about working with the auditory system is that the exact location in the cochlea at which a sound is perceived depends on the sound's frequency. High-pitched sounds register near the entrance of the cochlea, while low-pitched sounds are perceived much deeper inside. (One octave equates to about 3 millimeters of cochlear tube.) To test how effective our device is at delivering a drug, we can fill the device's reservoir with a drug that has a temporary dampening effect on hearing and begin pumping it into the subject's ear. When we observe that the drug is deadening only high-pitched sounds, we know that the drug has reached the entrance to the cochlea. Once the subject stops responding to low-frequency tones, we know that the drug has approached the apex of the coiled tube. And that's what happened—we literally watched the guinea pigs lose their hearing in a cascade of frequencies, first as the high-frequency hearing diminished, then as the lower-frequency hearing was lost.
We succeeded in demonstrating for the first time that the parameters of hearing can be modulated in a controlled manner using an engineered, preprogrammed delivery device. We also established a margin of safety within which drugs can be effectively delivered without damaging sensitive hearing structures. The downside of the device is that any drug supply will eventually be depleted, but we are optimistic that by the time the device is ready for market, we'll be able to implant at least a year's worth of a highly concentrated drug.
As is true with all implantable devices, one of the key challenges we still face is how to power the device. We envision one small battery that's implanted and one slightly larger battery that's either on the surface of the skin behind the ear or tucked just underneath the ear. This larger battery would be easily rechargeable and replaceable and could, in turn, wirelessly recharge the embedded battery.
There are many hurdles to overcome in the development of this or any other electronically controlled implantable drug-delivery system. These obstacles run the gamut from microfluidic challenges to surgical and biological considerations. Once these hurdles have been cleared, implantable drug-delivery devices ought to see a healthy future. With electronics taking the bulk of the work away from them, patients can look forward to healthier, simpler, and most of all, more enjoyable lives.
This article originally appeared in print as "Medicine By Micromachine."
IEEE Spectrum has agreed to include the following statement at the request of the authors. This article was updated 9 November 2009.
The project described was supported by Award Number R56DC006848 from the National Institute on Deafness and Other Communication Disorders. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About the Author
Jeffrey T. Borenstein’s first experience with the Massachusetts Eye and Ear Infirmary was as a patient in the hearing department. Three years later he started collaborating with MEEI on microfluidics-based drug delivery for the inner ear, a project he describes in ”Medicine by Micromachine”. A solid-state physicist at the Charles Stark Draper Laboratory, in Cambridge, Mass., Borenstein says he ”always had a fascination with medicine and wanted to find opportunities to get involved in human health.”
To Probe Further
The microfluidic technology described in this article is the product of a decade of research at Draper Laboratory, in Cambridge, Mass. Initially, the research was targeted toward lab-on-a-chip systems, a field that has experienced explosive growth and now has its own journal, Lab on a Chip, and an international annual conference, MicroTAS. In one early application, Draper’s microfluidic system was developed as a front end for a biosensor that could be used in medical applications, such as clinical diagnostics, or in biodefense. Mark Mescher and Jason Fiering have led the development of microfluidics at Draper, with contributions from Erin Swan, Sarah Tao, Ernest Kim, and Maria Holmboe.
The project on drug delivery for the inner ear got its start in 2002, when Draper and the Massachusetts Eye and Ear Infirmary, or MEEI, began a seed project aimed at developing new therapeutic approaches to sensorineural hearing loss. The MEEI is home to the Eaton-Peabody Laboratories (EPL), a 50-year-old institute devoted to hearing and deafness research. Three MEEI researchers—Sharon Kujawa, William Sewell, and Michael McKenna—have played key roles in developing the technology and finding ways to apply it to the treatment of inner-ear diseases. MEEI postdoctoral fellow Zhiqiang Chen conducted the first demonstration of the system in an animal model, and this work was published in the Journal of Controlled Release in 2005. More recent publications have described the device and its adaptation for an animal model. A review article on drug delivery in the inner ear and an overview of micro- and nanoscale technologies for drug delivery are also informative.
For a broader introduction to drug delivery, Mark Saltzman wrote an excellent textbook. To learn more about the early pioneering work of Robert Langer and his colleagues, see this article in the online version of Hopkins Medicine. MicroChips’ technology is described in several articles, including this one, published by MIT’s Technology Review.
The intracochlear drug delivery project is funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), an institute of the National Institutes of Health, in Bethesda, Md.
