Delivery of neurotrophin-3 to the cochlea using alginate beads
Delivery of neurotrophin-3 to the cochlea using alginate beads
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DOI：
10.1097/01.mao.0000169780.84588.a5
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发表时间：
2005-05-01
影响因子：
2.1
通讯作者：
O'Leary, S
中科院分区：
文献类型：
--
作者：
Noushi, F;Richardson, RT;O'Leary, S
目的：本研究的目的是设计一种新的耳蜗神经营养素（NT）传递系统的救援听觉神经元后耳毒性引起deading.Background：NT-3是一种营养生长因子，促进听觉神经的生存，并可能有一个潜在的治疗作用，在减缓神经元损失进行性耳聋，特别是作为一个辅助目前的人工耳蜗植入。由藻酸盐制成的珠子是可生物降解的缓释物质，可以放置在圆窗或耳蜗内。本研究考察了NT-3海藻酸盐微球的载药性能、释药动力学和植入潜力。方法：采用离子凝胶法制备海藻酸盐微球，后载NT-3。使用酶联免疫吸附测定法在5天内测量NT-3的释放。藻酸盐珠植入到rebuened豚鼠28天，之后的听觉神经元的生存assessed.Results：酶联免疫吸附试验研究表明，98%至99%的NT-3加载缓慢，部分释放超过5天的林格氏溶液。此外，向递送系统中添加肝素将NT-3释放调节为更小的模式。在豚鼠耳蜗中植入藻酸盐-肝素珠产生最小的局部组织反应。NT-3加载珠植入在圆窗和内鼓阶的基础转提供了显着的保护，从降解和凋亡的听觉神经元相比，卸载珠或未经处理的cochleae.Conclusions：这项研究表明藻酸盐珠是一个安全的，可生物降解的和有效的递送系统NT-3的耳蜗。
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.