A Novel Regulated Nanohydrogel Delivery System for Inner Ear Application

Abstract

Objectives: 1) Develop a novel chitosan-hydrogel-based nanoparticle delivery system (nanohydrogel) for inner ear application and to evaluate its structures and release kinetics in vitro. 2) Evaluate if the nanohydrogel delivery system can be turned off using an enzymatic regulator for inner ear delivery. 3) Evaluate the inner ear distribution of nanoparticles following round window membrane application in a mouse model. Methods: Nanoparticles labeled with fluorescence were constructed and loaded into a chitosan-based hydrogel to form a nanohydrogel delivery system. In vitro studies were performed to evaluate the thermosensitivity, structure, and nanoparticle release kinetics of the nanohydrogel with/without chitosanase enzymatic regulation. Morphologic studies were performed to evaluate the nanoparticle delivery and distribution within the inner ear structures in a mouse model. Results: After obtaining a homogeneous, viscous and thermosensitive nanohydrogel system, in vitro studies showed that the nanohydrogel can carry and release nanoparticles in a controlled and sustained manner, and chitosanase can effectively regulate this release if needed. A matrix-like ultrastructure containing nanosized particles was confirmed. In vivo findings further confirm that the nanohydrogel delivered nanoparticles into the perilymphatic system and reached cellular structures of the inner ear in our mouse model. Conclusions: Our study suggests that the nanohydrogel system has the potential to safely deliver drugs or biomaterials in a controlled and sustained manner for inner ear application. This system could be used for targeted therapy for inner ear diseases that require safe and non-invasive delivery approaches.