title: Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.
abstract: OBJECTIVE
  Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders.
  
  
  METHODS
  The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet.
  
  
  RESULTS
  Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal.
  
  
  CONCLUSIONS
  HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss.
authors.affiliation: Department of Clinical Neuroscience, Center for Hearing and Communication Research, Karolinska Institutet, Stockholm, Sweden. amanj.saber@ki.se
authors.forename: Amanj
authors.initials: A
authors.lastname: Saber
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
authors.forename: Tobias
authors.initials: T
authors.lastname: Bramer
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engmér
authors.forename: Mats
authors.initials: M
authors.lastname: Ulfendahl
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004427:Ear Diseases / Q000188:drug therapy; D007758:Ear, Inner / Q000378:metabolism; D004432:Ear, Middle / Q000378:metabolism; D005782:Gels; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D006820:Hyaluronic Acid / Q000494:pharmacology; D007267:Injections; D009355:Neomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D012405:Round Window, Ear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D005782:Gels; D014677:Pharmaceutical Vehicles; D006820:Hyaluronic Acid; D009355:Neomycin