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In parallel, Ca 2+ dysregulation, endoplasmic reticulum stress and mitochondrial dysfunction further exacerbate astrocytic impairment 114

In some embodiments, the use of multiparticulates (e.g., micronized particles) of a therapeutic agent, or an otic agent, allows for extended and/or sustained release of the therapeutic agent from any formulation described herein compared to a formulation or composition comprising non-multiparticulate (e.g., non-micronized) therapeutic agent

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