title: Local treatment of the inner ear: a study of three different polymers aimed for middle ear administration.
abstract: CONCLUSIONS
  A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination.
  
  
  OBJECTIVE
  Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration.
  
  
  METHODS
  The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection.
  
  
  RESULTS
  The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engmér Berglin
authors.forename: Pernilla
authors.initials: P
authors.lastname: Videhult Pierre
authors.forename: Andreas
authors.initials: A
authors.lastname: Ekborn
authors.forename: Tobias
authors.initials: T
authors.lastname: Bramer
authors.forename: Katarina
authors.initials: K
authors.lastname: Edsman
authors.forename: Malou
authors.initials: M
authors.lastname: Hultcrantz
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007758:Ear, Inner; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D006309:Hearing / Q000502:physiology*; D006320:Hearing Tests; D007267:Injections; D007759:Labyrinth Diseases / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D011108:Polymers / Q000008:administration & dosage*
chemical_list: D011108:Polymers
keywords: ABR; carboxymethyl cellulose; guinea pig; hyaluronan; intra-tympanic; morphology; poloxamer 407; polymer; targeted drug delivery; toxicity