State-of-the-art mechanisms of intracochlear drug delivery.
OBJECTIVE
Treatment of auditory and vestibular dysfunction has become increasingly dependent on inner ear drug delivery. Recent advances in molecular therapy and nanotechnology have pushed development of alternate delivery methodologies involving both transtympanic and direct intracochlear infusions. This review examines recent developments in the field relevant to both clinical and animal research environments.


RESULTS
Transtympanic delivery of gentamicin and corticosteroids for the treatment of Meniere's disease and sudden sensorineural hearing loss continues to be clinically relevant, with understanding of pharmacokinetics becoming more closely studied. Stabilizing matrices placed on the round window membrane for sustained passive delivery of compounds offer more controlled dosing profiles than transtympanic injections. Nanoparticles are capable of traversing the round window membrane and cochlear membranous partitions, and may become useful gene delivery platforms. Cochlear and vestibular hair cell regeneration has been demonstrated by vector delivery to the inner ear, offering promise for future advanced therapies.


CONCLUSIONS
Optimal methods of inner ear drug delivery will depend on toxicity, therapeutic dose range, and characteristics of the agent to be delivered. Advanced therapy development will likely require direct intracochlear delivery with detailed understanding of associated pharmacokinetics.
Borkholder
David A
DA
Department of Electrical Engineering, Rochester Institute of Technology, Rochester, NY 14623, USA. david.borkholder@rit.edu
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D005839:Gentamicins / Q000008:administration & dosage*; D003639:Hearing Loss, Sudden / Q000188:drug therapy; D006801:Humans; D015552:Injections, Intralesional; D008575:Meniere Disease / Q000188:drug therapy; D053758:Nanoparticles / Q000008:administration & dosage; D012680:Sensitivity and Specificity; D014432:Tympanic Membrane / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D005839:Gentamicins
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