title: Novel in vivo imaging analysis of an inner ear drug delivery system in mice: comparison of inner ear drug concentrations over time after transtympanic and systemic injections.
abstract: OBJECTIVE
  Systemic steroid injections are used to treat idiopathic sudden-onset sensorineural hearing loss (ISSHL) and some inner ear disorders. Recent studies show that transtympanic (TT) steroid injections are effective for treating ISSHL. As in vivo monitoring of drug delivery dynamics for inner ear is lacking, its time course and dispersion of drugs is unknown. Here, we used a new in vivo imaging system to monitor drug delivery in live mice and to compare drug concentrations over time after TT and systemic injections.
  
  
  METHODS
  Luciferin delivered into the inner ears of GFAP-Luc transgenic mice reacted with luciferase in GFAP-expressing cells in the cochlear spiral ganglion, resulting in photon bioluminescence. We used the Xenogen IVIS® imaging system to measure how long photons continued to be emitted in the inner ear after TT or systemic injections of luciferin, and then compared the associated drug dynamics.
  
  
  RESULTS
  The response to TT and IP injections differed significantly. Photons were detected five minutes after TT injection, peaking at ~20 minutes. By contrast, photons were first detected 30 minutes after i.p. injection. TT and i.p. drug delivery time differed considerably. With TT injections, photons were detected earlier than with IP injections. Photon bioluminescence also disappeared sooner. Delivery time varied with TT injections.
  
  
  CONCLUSIONS
  We speculate that the drug might enter the Eustachian tube from the middle ear. We conclude that inner-ear drug concentration can be maintained longer if the two injection routes are combined. As the size of luciferin differs from that of therapeutics like dexamethasone, combining drugs with luciferin may advance our understanding of in vivo drug delivery dynamics in the inner ear.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Keio University, Shinjuku-ku, Tokyo, Japan. skan@a7.keio.jp
authors.forename: Sho
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Masato
authors.initials: M
authors.lastname: Fujioka
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yasuda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hirotaka James
authors.initials: HJ
authors.lastname: Okano
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods*; D004432:Ear, Middle / Q000187:drug effects; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy*; D003639:Hearing Loss, Sudden / Q000188:drug therapy*; D015552:Injections, Intralesional; D051379:Mice; D008822:Mice, Transgenic; D014432:Tympanic Membrane / Q000187:drug effects*
chemical_list: D003907:Dexamethasone