Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane

被引:68
作者
Borden, Robert C. [1 ]
Saunders, James E. [1 ]
Berryhill, Wayne E. [1 ]
Krempl, Greg A. [1 ]
Thompson, David M. [2 ]
Queimado, Lurdes [1 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Otorhinolaryngol, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK 73104 USA
关键词
Inner ear disorders; Dexamethasone; Hyaluronic acid; Round window membrane; SENSORINEURAL HEARING-LOSS; INTRATYMPANIC STEROID TREATMENT; EAR DRUG-DELIVERY; GUINEA-PIG MODEL; INNER-EAR; MIDDLE-EAR; SODIUM HYALURONATE; SYSTEMIC THERAPY; RESIDUAL HEARING; SCALA TYMPANI;
D O I
10.1159/000313506
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
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
引用
收藏
页码:1 / 11
页数:11
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