A Novel Controlled Local Drug Delivery System for Inner Ear Disease
A Novel Controlled Local Drug Delivery System for Inner Ear Disease
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DOI：
10.1097/mlg.0b013e31815f8e41
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发表时间：
2008-04-01
期刊：
影响因子：
2.6
通讯作者：
Li, Daqing
中科院分区：
文献类型：
--
作者：
Paulson, David P.;Abuzeid, Waleed;Li, Daqing
目的：我们的目标是开发一种新型的药物输送系统，与目前的地塞米松或庆大霉素等药物给药方法相比，该系统可能会改善临床结局。该系统侧重于一个单一的局部应用程序，通过圆窗膜的内耳。假设：一个壳聚糖-甘油磷酸盐（CGP）-水凝胶为基础的药物输送系统可以被工程化，以提供局部和持续的药物release to the inner ear.Study Design：In vitro：药物释放和（CGP）-水凝胶基质降解的特点是使用地塞米松作为模型药物。体内：将载有地塞米松的CGP-水凝胶置于小鼠的圆窗龛中。从卵圆窗获得外淋巴样品并分析地塞米松。CGP-hydrogel对听觉功能的影响进行了评估。结果：在体外：一个CGP-hydrogel被设计为释放92%的地塞米松负载超过连续4天的水凝胶基质的同时降解。体内：在将CGP-水凝胶手术放置到圆窗龛后，我们检测到外淋巴液中地塞米松水平升高5天。听觉功能测试显示，在术后第10天，解决了暂时性的听力损失，在立即的手术后day.Conclusions：我们报告的发展，CGP-水凝胶，可生物降解的矩阵，实现局部，持续提供地塞米松的内耳。手术操作或对我们的鼠模型施用CGP-水凝胶没有导致显著的并发症。
Purpose: Our goal is to develop a novel drug delivery system that can potentially improve clinical outcomes compared to current methods of dosing drugs such as dexamethasone or gentamicin. This system focuses on a single local application to the inner ear via the round window membrane.Hypothesis: A chitosan-glycerophosphate (CGP)-hydrogel based drug delivery system can be engineered to provide local and sustained drug release to the inner ear.Study Design: In vitro: drug release and (CGP)-hydrogel matrix degradation were characterized using dexamethasone as a model drug. In vivo: dexamethasone laden CGP-hydrogel was placed in the round window niche of mice. Perilymph samples were obtained from the oval window and analyzed for dexamethasone. The impact of CGP-hydrogel on auditory function was evaluated.Results: In vitro: A CGP-hydrogel was designed to release 92% of the dexamethasone load over 4 consecutive days with concurrent degradation of the hydrogel matrix. In vivo: After surgical placement of CGP-hydrogel to the round window niche, we detected elevated levels of dexamethasone in perilymph for 5 days. Auditory function testing revealed a temporary hearing loss in the immediate postoperative period, which resolved by the 10th post-operative day.Conclusions: We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.