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    Delivery of neurotrophin-3 to the cochlea using alginate beads

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    Delivery of neurotrophin-3 to the cochlea using alginate beads (592.4Kb)

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    Author
    Noushi, Fanoosh; Richardson, Rachael T.; Hardman, Jennifer; Clark, Graeme M.; O'LEARY, STEPHEN
    Date
    2005
    Source Title
    Otology & Neurotology
    University of Melbourne Author/s
    Clark, Graeme; O'Leary, Stephen; Richardson, Rachael
    Metadata
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    Document Type
    Journal Article
    Citations
    Noushi, F., Richardson, R. T., Hardman, J., Clark, G. M., & O'Leary, S. (2005). Delivery of neurotrophin-3 to the cochlea using alginate beads. Otology & Neurotology, 26(3), 528-533.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/27622
    Description

    This is a publisher’s version of an article published in Otology & Neurotology 2005. This version is reproduced with permission of Lippincott Wilkins & Williams.

    Abstract
    Objective: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. Background: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutical role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can he placed at the round window or inside the cochlea. This study investigates the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. Methods: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which surviva1 of auditory neurons was assessed. Results: Enzyme-linked immunosorbent assay studies demonstrated a 98%: to 99% loading of NT-3 with a slow, partial release over 5 days in Ringers solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction NT-3 loaded beads implanted as both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. Conclusions: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.
    Keywords
    alginate; cochlea; drug delivery; neurotophin-3; sensorineural hearing loss

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