Regulated Chitosan-Based Inner-Ear Drug Delivery

Abstract

Objective: 1) To evaluate a novel system for regulating the chitosan-glycero-phosphate (CGP)-based hydrogel drug delivery to the inner ear. 2) To understand the distribution of gentamicin in the inner ear following CGP drug delivery with and without regulation.

Method: Chitosanase, specifically targeting CGP, was identified and purified for its use as a CGP regulation system. In vitro and in vivo studies were conducted to evaluate the effect of the chitosanase on the inner ear drug delivery and distribution. Gentamicin-Texas Red (GTTR) was used for tracking the drug distribution.

Results: Purified chitosanase was confirmed with Western blot. The in vitro study showed that the chitosanase-based regulation system effectively controlled the gentamicin releasing. The in vivo data concur with in vitro findings and demonstrated that the gentamicin concentration in the inner ear can be successfully regulated by applying the chitosanase. Moreover, the gentamicin inner ear distribution can also be regulated by changing its inner ear concentration.

Conclusion: Our study suggests that the chitosanase-based regulation system can be effectively used for controlled inner ear drug delivery. This system has a potential to stop inner ear drug application when side effects or drug-related toxicities start to occur and should be used for safe drug application in the inner ear.