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庆大霉素经壳聚糖甘油磷酸盐水凝胶递送系统局部给药后在内耳中的分布。

Distribution of gentamicin in inner ear after local administration via a chitosan glycerophosphate hydrogel delivery system.

作者信息

Luo Jianfen, Xu Lei

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan, People's Republic of China.

出版信息

Ann Otol Rhinol Laryngol. 2012 Mar;121(3):208-16. doi: 10.1177/000348941212100311.

DOI:10.1177/000348941212100311
PMID:22530482
Abstract

OBJECTIVES

We examined the distribution of gentamicin sulfate in the inner ear after delivery via a chitosan glycerophosphate (CGP) hydrogel system and examined the change in morphology of the hair cells so as to determine how gentamicin affected the function of the inner ear.

METHODS

A matrix of CGP hydrogel loaded with gentamicin conjugated with Texas Red (GTTR) was injected into the round window niche of the left ear of C57/BL6 mice. The mice were painlessly killed on day 1 or day 7 after injection. Confocal fluorescence microscopy was used to locate the gentamicin in the cochlear and vestibular systems.

RESULTS

In the vestibule, the intensity of GTTR staining in the hair cells of the macula of the saccule on day 1 was significantly stronger than that on day 7, and the number of hair cell bundles on top of the cuticular plate on day 7 was obviously decreased in comparison to that on day 1. In the cochlea, the intensity of GTTR staining in the basal turn was significantly stronger than that in the medial turn on both day 1 and day 7. Negligible fluorescence was observed in the apical turn on both day 1 and day 7. Less-intense GTTR staining was detected on day 7 than on day 1 in both the basal turn and the medial turn. There was some outer hair cell loss in the basal turn on day 7, and no hair cell loss in the medial and apical turns at any time point.

CONCLUSIONS

Gentamicin is distributed in the inner ear via the CGP hydrogel delivery system in a time-dependent and basal-to-apical manner. This finding implies that the vestibule and the basal turn may retain more gentamicin for a longer period than do other sites in the inner ear. These two characteristics may account for the high-frequency hearing loss and vestibular dysfunction seen with use of this system to deliver gentamicin into the inner ear.

摘要

目的

我们通过壳聚糖甘油磷酸酯(CGP)水凝胶系统研究了分娩后硫酸庆大霉素在内耳中的分布,并研究了毛细胞形态的变化,以确定庆大霉素如何影响内耳功能。

方法

将负载与德克萨斯红(GTTR)偶联的庆大霉素的CGP水凝胶基质注射到C57/BL6小鼠左耳的圆窗龛中。在注射后第1天或第7天无痛处死小鼠。使用共聚焦荧光显微镜在内耳和前庭系统中定位庆大霉素。

结果

在前庭中,第1天球囊斑毛细胞中GTTR染色强度明显强于第7天,与第1天相比,第7天角质板顶部的毛细胞束数量明显减少。在耳蜗中,第1天和第7天基底转中GTTR染色强度均明显强于中阶。在第1天和第7天,顶转均观察到可忽略不计的荧光。第7天基底转和中阶的GTTR染色强度均低于第1天。第7天基底转有一些外毛细胞丢失,在任何时间点中阶和顶转均无毛细胞丢失。

结论

庆大霉素通过CGP水凝胶递送系统以时间依赖性和从基底到顶部的方式在内耳中分布。这一发现意味着前庭和基底转可能比内耳中的其他部位保留更多的庆大霉素更长时间。这两个特征可能解释了使用该系统将庆大霉素递送至内耳时出现的高频听力损失和前庭功能障碍。

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