Silk-coated dexamethasone non-spherical microcrystals for local drug delivery to inner ear

The local drug delivery systems play an important role in treating sudden sensorineural hearing loss. In this work, we synthesized dexamethasone microcrystals (DEX MCs) using precipitation technique followed by silk coating via layer-by-layer assembly. Compared to raw DEX, the physicochemical properties including shape, crystal form, dispersity, dissolution or sustained release, of DEX MCs or poly-l-lysine/silk fibroin (PLL/SF) multilayers-coated DEX MCs (DEX-(PLL/SF)₃) were investigated. More importantly, after a single intratympanic administration in guinea pigs, DEX-(PLL/SF)₃ was uniformly distributed on the round window membrane (RWM) in comparison with raw DEX and DEX MCs. And increased concentration of DEX treatment resulted in higher perilymph DEX levels. No significant morphological change and inflammatory responses on the cochlear tissue were observed. Thus, the DEX-(PLL/SF)₃ formulation could be a novel local drug delivery strategy to realize safe, efficient and sustainable DEX delivery into inner ear across RWM.