title: Development of a microfluidics-based intracochlear drug delivery device.
abstract: BACKGROUND
  Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration.
  
  
  METHODS
  We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions.
  
  
  RESULTS
  We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters.
  
  
  CONCLUSIONS
  We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. wfs @ epl.meei.harvard.edu
authors.forename: William F
authors.initials: WF
authors.lastname: Sewell
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Borenstein
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Jason
authors.initials: J
authors.lastname: Fiering
authors.forename: Ophir
authors.initials: O
authors.lastname: Handzel
authors.forename: Maria
authors.initials: M
authors.lastname: Holmboe
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Kim
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Kujawa
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKenna
authors.forename: Mark M
authors.initials: MM
authors.lastname: Mescher
authors.forename: Brian
authors.initials: B
authors.lastname: Murphy
authors.forename: Erin E Leary
authors.initials: EE
authors.lastname: Swan
authors.forename: Marcello
authors.initials: M
authors.lastname: Peppi
authors.forename: Sarah
authors.initials: S
authors.lastname: Tao
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D006168:Guinea Pigs; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D010498:Perilymph / Q000187:drug effects*