Paper

Principles of Local Drug Delivery to the Inner Ear
Alec N. Salt^a, Stefan K. Plontke<sup>b

a</sup>Department of Otolaryngology, Washington University School of Medicine, St. Louis, Mo., USA;
^bDepartment of Otorhinolaryngology, Head and Neck Surgery and Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany

Address of Corresponding Author

Audiol Neurotol 2009;14:350-360 (DOI: 10.1159/000241892)

  Key Words

• Animal
• Cochlea
• Perilymph
• Controlled release
• Inner ear
• Human
• Local drug delivery
• Pharmacokinetics

  Abstract

As more and more substances have been shown in preclinical studies to be capable of preventing damage to the inner ear from exposure to noise, ototoxic drugs, ischemia, infection, inflammation, mechanical trauma and other insults, it is becoming very important to develop feasible and safe methods for the targeted delivery of drugs to specific regions in the inner ear. Recently developed methods for sampling perilymph from the cochlea have overcome major technical problems that have distorted previous pharmacokinetic studies of the ear. These measurements show that drug distribution in perilymph is dominated by passive diffusion, resulting in large gradients along the cochlea when drugs are applied intratympanically. Therefore, in order to direct drugs to specific regions of the ear, a variety of delivery strategies are required. To target drugs to the basal cochlear turn and vestibular system while minimizing exposure of the apical cochlear turns, single one-shot intratympanic applications are effective. To increase the amount of drug reaching the apical cochlear turns, repeated intratympanic injections or controlled-release drug delivery systems, such as biodegradable biopolymers or catheters and pumps, are more effective. However, if the applied substance does not easily pass through the round window membrane, or if a more widespread distribution of drug in the ear is required, then intralabyrinthine injections of the substance may be required. Intralabyrinthine injection procedures, which are currently in development in animals, have not yet been proven safe enough for human use.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Dr. Alec N. Salt
Department of Otolaryngology, Box 8115
Washington University School of Medicine
660 South Euclid Avenue, St. Louis, MO 63110 (USA)
Tel. +1 314 362 7560, Fax +1 314 362 1618, E-Mail salta@ent.wustl.edu

  Article Information

A.N.S. and S.K.P. contributed equally to this paper. A.N.S. is a member of the scientific advisory board of Otonomy; however, this work was not supported by Otonomy.

Received: April 1, 2009
Accepted after revision: July 17, 2009
Published online: November 16, 2009
Number of Print Pages : 11
Number of Figures : 5, Number of Tables : 0, Number of References : 84