Julie Sircoglou1, Maria Gehrke, Meryem Tardivel, Florence Siepmann, Juergen Siepmann, Christophe Vincent. 1. *Otology and Neurotology Department, University Hospital of Lille (CHRU), Salengro Hospital †Controlled Drug Delivery Systems and Biomaterials, INSERM U 1008 ‡BICeL, BioImaging Center Lille-Nord de France, School of Medicine, University of Lille 2, Lille, France.
Abstract
HYPOTHESIS: The purpose of this study was to develop a new strategy to deliver drugs to the inner ear from dexamethasone (DXM)-loaded silicone implants and to evaluate the distribution of the drug in the cochlea with confocal microscopy. BACKGROUND: Systemic drug administration for the treatment of inner ear disorders is tricky because of the blood-cochlear barrier, a difficult anatomical access, the small size of the cochlea, and can cause significant adverse effects. An effective way to overcome these obstacles is to administer drugs locally. METHODS: In vitro, the drug release from DXM-loaded silicone-based thin films and tiny implants into artificial perilymph was thoroughly analyzed by high-performance liquid chromatography. In vivo, a silicone implant loaded with 10% DXM and 5% polyethylene glycol 400 was implanted next to the stapes's footplate of gerbils. Delivery of DXM into the inner ear was proved by confocal microscopy imaging of the whole cochlea and the organ of Corti. RESULTS: The study showed a continuous and prolonged release during 90 days in vitro. This was confirmed by confocal microscopy that allowed detection of DXM by fluorescence labeling in the cell body of the hair cells for at least 30 days. Interestingly, fluorescence was already observed after 20 minutes of implantation, reached a climax at day 7, and could still be detected 30 days after implantation. CONCLUSIONS: Thus, we developed a new device for local corticosteroids delivery into the oval window with an extended drug release of DXM to the inner ear.
HYPOTHESIS: The purpose of this study was to develop a new strategy to deliver drugs to the inner ear from dexamethasone (DXM)-loaded silicone implants and to evaluate the distribution of the drug in the cochlea with confocal microscopy. BACKGROUND: Systemic drug administration for the treatment of inner ear disorders is tricky because of the blood-cochlear barrier, a difficult anatomical access, the small size of the cochlea, and can cause significant adverse effects. An effective way to overcome these obstacles is to administer drugs locally. METHODS: In vitro, the drug release from DXM-loaded silicone-based thin films and tiny implants into artificial perilymph was thoroughly analyzed by high-performance liquid chromatography. In vivo, a silicone implant loaded with 10% DXM and 5% polyethylene glycol 400 was implanted next to the stapes's footplate of gerbils. Delivery of DXM into the inner ear was proved by confocal microscopy imaging of the whole cochlea and the organ of Corti. RESULTS: The study showed a continuous and prolonged release during 90 days in vitro. This was confirmed by confocal microscopy that allowed detection of DXM by fluorescence labeling in the cell body of the hair cells for at least 30 days. Interestingly, fluorescence was already observed after 20 minutes of implantation, reached a climax at day 7, and could still be detected 30 days after implantation. CONCLUSIONS: Thus, we developed a new device for local corticosteroids delivery into the oval window with an extended drug release of DXM to the inner ear.
Authors: Ricardo Ferreira Bento; Fabiana Danieli; Ana Tereza de Matos Magalhães; Dan Gnansia; Michel Hoen Journal: Int Arch Otorhinolaryngol Date: 2016-02-16