Novel self-degradable prodrug blend thermogel for intratympanic drug delivery to treat inner ear diseases

The use of injectable hydrogel formulations for targeted drug delivery into the inner ear has gained considerable interest. In this study, we introduce a novel self-degradable prodrug blend thermogel system designed to deliver the anti-inflammatory drug, dexamethasone (DEX), in a controlled and safe manner for effective treatment of inner ear diseases. Our approach involves blending a thermogelling polymer, hexanoyl glycol chitosan (HGC), with a polymer prodrug, dexamethasone conjugated glycol chitosan (GC-DEX), to create injectable formulations suitable for intratympanic administration. Through extensive evaluation of the physicochemical and biological properties, we demonstrate that our thermogel formulations exhibit not only excellent thermogelling and injectable characteristics but also controlled release properties, resulting in enhanced drug absorption and prolonged drug concentration in the inner ear. The in vivo T2-weighted MRI Imaging further confirms the long-lasting stability of our thermogel formulations within the tympanic cavity, with a self-degradation period of approximately one month. Notably, guinea pigs treated with the HGC/GC-DEX formulation showed significant hearing recovery merely 7 days after noise exposure, accompanied by a reduction in outer hair cell loss. These promising results indicate the potential of our prodrug blend thermogel as an efficient delivery system for therapeutic agents in the inner ear.