Delivery of neurotrophin-3 to the cochlea using alginate beads

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.