Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

Local drug delivery has become an effective method for disease therapy in fine organs including ears, eyes, and noses. However, the multiple anatomical and physiological barriers, unique clearance pathways, and sensitive perceptions characterizing these organs have led to suboptimal drug delivery efficiency. Here, we developed dexamethasone sodium phosphate-encapsulated gelatin methacryloyl (Dexsp@GelMA) microgel particles, with finely tunable size through well-designed microfluidics, as otic drug delivery vehicles for hearing loss therapy. The release kinetics, encapsulation efficiency, drug loading efficiency, and cytotoxicity of the GelMA microgels with different degrees of methacryloyl substitution were comprehensively studied to optimize the microgel formulation. Compared to bulk hydrogels, Dexsp@GelMA microgels of certain sizes hardly cause air-conducted hearing loss in vivo. Besides, strong adhesion of the microgels on the round window membrane was demonstrated. Moreover, the Dexsp@GelMA microgels, via intratympanic administration, could ameliorate acoustic noise-induced hearing loss and attenuate hair cell loss and synaptic ribbons damage more effectively than Dexsp alone. Our results strongly support the adhesive and intricate microfluidic-derived GelMA microgels as ideal intratympanic delivery vehicles for inner ear disease therapies, which provides new inspiration for microfluidics in drug delivery to the fine organs.