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Michael DeSalvio, John Chi, Michael
Nguyen, Kevin Ip, Khine Win
Routes of Entry
Two routes of entry into ear
• systemic route: drug circulates through blood stream
• Applied locally to inner ear (targeted drug delivery)
www.gizmowatch.com
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
Chemotherapy Drug Delivery
• Reduce toxic effects of chemotherapy drugs through local delivery
• Use for middle ear cancers and tumors
• Use in conjunction with surgery to deliver antibiotics
Planelle-Casas, et al. TRP Channel Trafficking.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=frtrp&part=ch23
How is it Different?
•
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
Thehearinginstitute.org
Questions
Components
One or more microphones
Speech processor (noise cancellation)
Transmitter via electromagnetic induction
Receiver and stimulator
Array of 24 electrodes inter-woven through the cochlea
Michael N
Modification to Treat TRPML3 Mutation
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
Processor
Magnetic Coil
Mike D
Reservoir
Important Considerations
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.
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.
Khine
How does it work?
• 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.
Khine
Why is it beneficial?
• 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
Michael N
Disadvantages of 2nd method
•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
Kevin
Questions?