1. Michael DeSalvio, John Chi, Michael Nguyen, Kevin Ip, Khine Win

2. Two routes of entry into ear systemic route: drug circulates through blood stream Applied locally to inner ear (targeted drug delivery) Routes of Entry www.gizmowatch.com

3. Conventional Implant Technology As of 2009, 188,000 worldwide received implants. (Davis, J 2009 Peoria Journal) Approx 1 in 68 or 1.47% or 4 million people in USA 30,000 adults and 30,000 children (Marcus, M 2008 USA Today) FDA approved in 1984 Cochlear Implants rely on electrical connections to auditory nerve, destroying existing structures in the ear Developed by Cochlear Limited Austrailia

4. Chemotherapy Drug Delivery Planelle-Casas, et al. TRP Channel Trafficking. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=frtrp&part=ch23 A419P Reduce toxic effects of chemotherapy drugs through local delivery Use for middle ear cancers and tumors Use in conjunction with surgery to deliver antibiotics

5. Does not remove vestibular hair cells http://www.surgeryencyclopedia.com/C e-Fi/Cochlear-Implants.html Delivers chemotherapy drug treatment Measures levels of proteins in the cochlea through microfluidic pump with reversible catheter flow How is it Different? Thehearinginstitute.org

6. Questions

7. One or more microphones Speech processor (noise cancellation) Transmitter via electromagnetic induction Receiver and stimulator Array of 24 electrodes inter-woven through the cochlea Components Michael N

8. TRPML3 mutation disrupts the ion channel which allows too much Ca+ to enter cell Results in premature apoptosis Utilizing the device will re-train the auditory complex in the brain Simultaneously deliver calcium channel blockers Prevents premature cell death Modification to Treat TRPML3 Mutation Reservoir Processor Magnetic Coil Mike D

9. Concentration is key to limit the volume being released. Duration that the drug solution remains in contact with the hair cells. Number of times the drug application is repeated. Method of application, specifically whether injection is performed “blindly” through the tympanic membrane; through a microotoscope (Plontke et al., 2002a) after visualizing the RWM and removing the “false” membranes that occur in 30% of patients (Alzamil & Linthicum, 2000); or by application through an implanted cannula.Plontke et al., 2002aAlzamil & Linthicum, 2000 Background medium of the drug-containing solution, which may potentially influence the permeability properties of the cells of the RWM. Properties such as the osmolarity, pH, and ionic composition are likely to influence the properties of cells that the solution contacts. Important Considerations Khine

10. Injecting solution containing aminoglycoside into the middle ear space so that it contacts the round window membrane (RWM) of the cochlea. A small catheter will deliver the drug specifically to the hair cells within the Cochlea. Allows a way to analyze drug concentration in the ear and test for diagnostic progress non-invasively. How does it work? Khine

11. Can re-stimulate portions of the brain responsible for hearing even after prolonged “atrophy.” Documented patient Baron Jack Ashley, UK House of Lords Can improve hearing after complete deafness Reliable and efficient, long life cycle Restore hearing without damaging structures in ear canal Targeted drug delivery which mitigates drug exposure to other tissues Site specific target allows for precise calculation of dosage Why is it beneficial? Michael N

12. Suppress vestibular (balance) system function—with sometimes only minor effects on hearing. Risk of developing meningitis General risk of infection Cost: $45,000- $150,000 total cost Disadvantages of 2 nd method Kevin

13. Questions?