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In some embodiments, the pH of any formulation or composition described herein is designed to be compatible with the targeted otic structure (e.g., endolymph, perilymph or the like)

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23 NADPH is also needed for dihydrofolate reductase (DHFR) enzyme to catalyze the reduction of dihydrofolate to tetrahydrofolate (THF) in folate metabolism, which is required for de novo biosynthesis of thymidylate, purines, methionine, and some amino acids