Intracochlear drug delivery in combination with cochlear implants

Abstract

Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., for delivery of glucocorticosteroids, antiapoptotic substances, or neurotrophins to the inner ear. The performance of cochlear implants may thus be improved by protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can also be achieved by use of a biocompatible, resorbable controlled-release drug-delivery system. Two case reports for intracochlear controlled release drug delivery in combination with cochlear implants are presented. In order to treat progressive reduction in speech discrimination and increased impedance, two cochlear implant patients successfully underwent intracochlear placement of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using a computer model. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies.

Role of Glucocorticoids in Hearing Preservation in Partial Deafness Treatment

“…Both substances were administrated intravenously 60 min before implantation. As a final conclusion, authors stressed that dexamethasone could reduce scarring process as the electrode negotiated the hook region or near the electrode tip, but they did not observe the relation between dexamethasone and reduction of fibrosis relating to cochleostomy [13]. In vitro studies showed the correlation between reduction (loss) of auditory cells after exposure to tumor necrosis factor alpha (TNF-alpha) and dexamethasone-releasing polymer used to coat electrode of cochlear implant carries.…”

“…Two main groups of drugs are used in clinical practice: aminoglycoside (mainly gentamicin) in pharmacotherapy of Meniere's disease [10] and corticosteroids (dexamethasone, triamcinolone and dexamethasone) in pharmacotherapy of idiopathic sudden sensorineural hearing loss (ISSHL) and other cases of acute hearing loss [11]. The inner ear from a pharmacokinetic point of view is a multicompartment model [12,13] with stable fluids and balance between them (due to the presence of blood-labyrinth barrier (BLB)). Distribution process depends on many different factors such as route of administration, model of administration (single or repeated administration), dose of medicine, ionic composition, and pH or osmolarity of solution.…”

“…The main advantages of local drug delivery are as follows: Local drug administration may involve intracochlear administration (e.g., stem cell, gene therapy) or extracochlear administration (e.g., intratympanic injection). A combination of both routes of drug delivery to the ear is also possible [13]. According to publications, systemic administration in treatment of otorhinolaryngological diseases is known as noninvasive route of drug delivery, due to lack of damaging of tympanic membrane.…”

Introductory Chapter - Genealogy of Audiology

“…Important aspects of novel hearing restoration strategies including gene therapy [3], stem cells [4,5], and related intracochlear distribution nanotechnologies [6,7] are still at best in a preclinical phase.…”

Local drug delivery to the inner ear: Principles, practice, and future challenges

“…Nevertheless, many open questions exist in relation to drug delivery the ear. They include (adapted from Salt and Plontke, 2009 and Plontke et al 2017): 1) choice of drug, 2) choice of delivery strategy (systemic, local intratympanic, local intracochlear / intralabyrinthine, combined local and systemic, or directly via an auditory implant); 3) timing of application, including the consideration of chronopharmacological issues especially for drugs with short half-lives (Canlon 2018); 4) choice of formulation and/or drug carrier; 5) choice of drug delivery system; 6) dose to apply; 7) risk–benefit ratio of the therapy; and 8) obstacles to successfully test a promising candidate therapy in a clinical trial.…”