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

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.