title: In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants.
abstract: Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks. In the in vivo experiment, silicone rods loaded with 2 or 10 % dexamethasone, respectively, were implanted into the scala tympani of guinea pigs. Perilymph concentrations were measured during the first week after implantation. The results showed that dexamethasone was released from the silicone in a sustained manner. After a burst release, perilymph concentration was similar for silicone incorporated with 2 and 10 % dexamethasone, respectively. The similar pharmacokinetic profile was found in the in vitro experiment. The period of sustained drug delivery was maintained for 20 weeks in vitro and for 1 week in vivo. The results of the present study suggest that drugs like dexamethasone are released in a controlled manner from silicon electrode carriers of cochlear implants. Further studies will identify optimal release profiles for the use with cochlear implants to improve their safety and long-term performance.
authors: Department of Otolaryngology, Head and Neck Surgery, Beijing Naval General Hospital, Beijing, 100048, People's Republic of China.
authors: Ya
authors: Y
authors: Liu
authors: Electrode Research Section, MED-EL Medical Electronics, Innsbruck, Austria.
authors: Claude
authors: C
authors: Jolly
authors: MED-EL Deutschland GmbH, Starnberg, Germany.
authors: Susanne
authors: S
authors: Braun
authors: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors: Thomas
authors: T
authors: Stark
authors: Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors: Elias
authors: E
authors: Scherer
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors: Stefan K
authors: SK
authors: Plontke
authors: HNO-Zentrum, Neupfarrplatz 12/II, 93047, Regensburg, Germany. Jn.Kiefer@googlemail.com.
authors: Jan
authors: J
authors: Kiefer
mesh_terms: D000818:Animals; D019929:Cochlear Implantation; D003054:Cochlear Implants; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D034381:Hearing Loss / Q000601:surgery; D006801:Humans; D010498:Perilymph / Q000378:metabolism; D012533:Scala Tympani / Q000601:surgery; D012828:Silicones
chemical_list: D005938:Glucocorticoids; D012828:Silicones; D003907:Dexamethasone
keywords: Cochlear implant; Dexamethasone; Drug delivery; Inner ear; Pharmacokinetics