Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane
Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane
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DOI：
10.1159/000313506
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发表时间：
2011-01-01
影响因子：
1.6
通讯作者：
Queimado, Lurdes
中科院分区：
文献类型：
--
作者：
Borden, Robert C.;Saunders, James E.;Queimado, Lurdes
背景资料：使用鼓室内（IT）类固醇治疗内耳疾病是有希望的，但长期中耳药物应用的临床挑战已被证明是沉重的，并且尚未开发可持续的递送系统。方法：在这项研究中，豚鼠模型用于确定地塞米松与透明质酸（HA）基水凝胶的组合是否是一种有效、稳定和可持续的地塞米松内耳递送系统。对于每只动物，随机选择右侧和左侧中耳泡，仅用地塞米松或地塞米松-HA（Dex-HA）凝胶填充。在不同时间点收集外淋巴样品，并使用ELISA测定地塞米松水平。结果：地塞米松是可测量的外淋巴样品治疗后72小时。在治疗后24小时，用Dex-HA凝胶治疗的耳中的外淋巴液地塞米松浓度显著高于（p = 0.01）仅用地塞米松治疗的耳。虽然外淋巴液地塞米松浓度在用Dex-HA凝胶处理后48小时降低，但该水平仍高于仅用地塞米松处理的耳中在24小时观察到的水平。在样品之间观察到地塞米松浓度的高度变异性，并且接受不同治疗的匹配耳朵之间的变异性显著低于每个治疗组内的变异性，表明个体参数可能在外淋巴液地塞米松浓度中起主要作用。地塞米松浓度与性别、体重或偏侧性之间无统计学显著相关性。结论：我们的研究结果表明，本研究中使用的Dex-HA凝胶提供了一种有效和持续的地塞米松释放机制，可用于治疗突发性感音神经性听力损失等疾病。这可能会降低与IT治疗相关的发病率和成本。版权所有（C）2010 S. Karger AG，巴塞尔
Background: The use of intratympanic (IT) steroids for the treatment of inner ear disorders is promising, but the clinical challenges of prolonged middle ear drug application have proven burdensome, and a sustainable delivery system is yet to be developed. Method: In this study, a guinea pig model was used to determine if dexamethasone in combination with a hyaluronic-acid (HA)-based hydrogel is an efficient, stable and sustainable dexamethasone delivery system to the inner ear. For each animal, right and left middle ear bullae were randomly selected to be filled with dexamethasone alone or dexamethasone-HA (Dex-HA) gel. Perilymph samples were collected at different time points and dexamethasone levels were determined using an ELISA. Results: Dexamethasone was measurable in the perilymph samples up to 72 h after treatment. At 24 h after treatment, the perilymph dexamethasone concentrations were significantly higher (p = 0.01) in the ears treated with Dex-HA gel than in those treated with dexamethasone alone. While the perilymph dexamethasone concentration had decreased at 48 h after treatment with Dex-HA gel, the levels were still higher than those observed at 24 h in ears treated with dexamethasone alone. A high variability in dexamethasone concentration was observed between the samples, and the variability between matched ears receiving different treatments was remarkably lower than the variability within each treatment group, suggesting that individual parameters might play a major role in perilymph dexamethasone concentration. There was no statistically significant correlation between dexamethasone concentration and sex, weight or laterality. Conclusions: Our results show that the Dex-HA gel used in this study provides an effective and sustained dexamethasone release mechanism that might be utilized to treat conditions such as sudden sensorineural hearing loss. This could potentially reduce the morbidity and costs associated with IT treatment. Copyright (C) 2010 S. Karger AG, Basel