Local Delivery of Therapeutics to the Inner Ear: The State of the Science

Abstract

Background: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics.Methods: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently.Results: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker.Conclusion: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics.

Development and in vivo validation of small interfering RNAs targeting NOX3 to prevent sensorineural hearing loss

“…Inner ear delivery of therapeutics represents an important challenge nowadays (28,29). The aforementioned, fluorescently conjugated siRNA (siGLO), was used to compare the middle ear and direct inner ear delivery in the mouse model in vivo (Figure 6A).…”

Current Strategies to Combat Cisplatin-Induced Ototoxicity

“…The alternative to systemic administration is local drug delivery, which mainly includes intratympanic and intracochlear/ intralabyrinthine delivery (Anderson et al, 2019). Advantages of local delivery include passage through the blood-labyrinth barrier, acquisition of higher drug concentration in the cochlea, and avoidance of "first-pass" metabolism (Plontke et al, 2014).…”

The Clinical Effect of Steroids for Hearing Preservation in Cochlear Implantation: Conclusions Based on Three Cochlear Implant Systems and Two Administration Regimes

“…Information from two of the world’s foremost agencies responsible for drug authorization—the Food and Drug Administration (FDA) and the European Medical Agency (EMA)—indicate that there is no drug or medical device approved for delivery direct to the inner ear. There are some options for delivering drugs intracochlearly (via the oval or round window through injection, catheter/micropump, stapes surgery, or cochlear implant), although these are largely restricted to animal studies and prototypes [ 8 , 9 ]. There are thus two possibilities for delivering drugs to the inner ear: systemic or local.…”