Delivery of neurotrophin-3 to the cochlea using alginate beads.
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 therapeutic 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 be placed at the round window or inside the cochlea. This study investigated 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 survival 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 Ringer's 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 at 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.
Noushi
Farnoosh
F
University of Melbourne, Department of Otolaryngology, East Melbourne, Australia.
Richardson
Rachael T
RT
Hardman
Jennifer
J
Clark
Graeme
G
O'Leary
Stephen
S
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D002470:Cell Survival; D003051:Cochlea / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D003056:Cochlear Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003638:Deafness / Q000139:chemically induced / Q000503:physiopathology*; D007758:Ear, Inner / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D016057:Evoked Potentials, Auditory, Brain Stem; D020723:Glucuronic Acid; D006168:Guinea Pigs; D006603:Hexuronic Acids; D008863:Microspheres; D009475:Neurons, Afferent / Q000187:drug effects; D020933:Neurotrophin 3 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014118:Toxins, Biological
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020933:Neurotrophin 3; D014118:Toxins, Biological; D020723:Glucuronic Acid