title: In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.
abstract: Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.
authors.affiliation: Department of Otolaryngology, Hannover School of Medicine, Hannover, Germany; University of Veterinary Medicine Hannover, Foundation, Institute of Zoology, Hannover, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Hütten
authors.affiliation: MED-EL Innsbruck, Research & Development, Innsbruck, Österreich; Interactive Materials Research-DWI e.V. and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.
authors.forename: Anandhan
authors.initials: A
authors.lastname: Dhanasingh
authors.affiliation: MED-EL Innsbruck, Research & Development, Innsbruck, Österreich.
authors.forename: Roland
authors.initials: R
authors.lastname: Hessler
authors.affiliation: J.W. Goethe University Hospital and Faculty of Medicine, Department of Otolaryngology, Frankfurt am Main, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Stöver
authors.affiliation: University of Veterinary Medicine Hannover, Foundation, Institute of Zoology, Hannover, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Esser
authors.affiliation: Interactive Materials Research-DWI e.V. and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Möller
authors.affiliation: Department of Otolaryngology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lenarz
authors.affiliation: MED-EL Innsbruck, Research & Development, Innsbruck, Österreich.
authors.forename: Claude
authors.initials: C
authors.lastname: Jolly
authors.affiliation: Interactive Materials Research-DWI e.V. and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany; University of Würzburg, Department of Functional Materials in Medicine and Dentistry, Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Groll
authors.affiliation: Department of Otolaryngology, Hannover School of Medicine, Hannover, Germany; Institute of Audioneurotechnology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Scheper
mesh_terms: D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000295:instrumentation*; D007758:Ear, Inner / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008297:Male; D012825:Silicon / Q000737:chemistry
chemical_list: D005938:Glucocorticoids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D012825:Silicon
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