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Local Drug Delivery to the Inner Ear
Built from Haynes-Glasscock-Shambaugh Surgery of the Ear, Seventh Edition
What’s inside
9 sections · 104 slides
Overview
- Scope of this topic
Rationale for Local Delivery
- Two categories of inner ear drug delivery
- Volume mismatch between body and perilymph
- Anatomic connections of the inner ear
- Anatomy of the internal ear
- Systemic versus local therapy
- Middle ear as a drug reservoir
Transtympanic Delivery Technique
- Route of administration through the drum
- Anatomic basis of middle ear drug delivery
- Local anaesthesia of the tympanic membrane
- Phenol application and single-use applicators
- Duration of patency of the myringotomy
- Refinements of the myringotomy technique
- Needle selection and injection volume
- Injection technique and post-procedure care
- Sequence of a transtympanic injection
Anatomic Considerations for Entry
- Routes of diffusion into the inner ear
- Three-layered structure of the round window membrane
- Factors determining round window permeability
- Obstruction of the round window niche
- Anatomical variation and human pharmacokinetic data
- Orientation of the round window in the upright patient
- Strategies to improve round window transfer
- Predicting permeability from molecular properties
- Carrier systems for round window delivery
Distribution and Clearance in Perilymph
- Modelling distribution of medication in the inner ear
- Absorption through the otic capsule
- The stapediovestibular ligament as a delivery route
- Passive diffusion within the scala tympani
- Cochlear duct in cross section
- Molecular weight and apical penetration
- Elimination of drug from the cochlea
- Devices to prolong round window contact
Intrascalar Therapy
- Rationale for direct intrascalar injection
- Evidence that the inner ear tolerates instrumentation
- The endolymphatic sac as a delivery site
- Human gadolinium data from the endolymphatic sac
- Cochlear implant candidates as a study population
- Drug delivery channels within the electrode array
- Cochlear implant components
- Catheter-based intrascalar delivery in humans
- Novel drug delivery devices for use in the ear
- The reciprocating pump concept
- Indications and risks of long-term pump delivery
Medications in Current Clinical Use
- Agents delivered locally to the inner ear
- Streptomycin and the origins of ablative therapy
- Evolution of intratympanic gentamicin protocols
- Current gentamicin dosing and pre-treatment assessment
- Indications for intratympanic steroids
- Steroids in Meniere's disease
- Improving dexamethasone availability at the membrane
- Thermosensitive polymer steroid formulations
- Intratympanic steroids in sudden hearing loss
- Comparative evidence for the intratympanic route
- Limitations of the steroid meta-analyses
- Steroids in cochlear implantation
- Preoperative steroids and unresolved timing
- Cochlear NMDA receptors and tinnitus
- Hyaluronic acid gel formulation of NMDA blockers
- Apoptosis modulation in noise and ototoxic injury
- Human data on the Jnk inhibitor AM 111
- Antioxidants for ototoxicity and noise trauma
- Trade-offs of local otoprotection during chemotherapy
The Future of Inner Ear Delivery
- Why biologics require direct intrascalar delivery
- Rationale for inner ear gene therapy
- Atoh1 and the specification of hair cells
- Human vector administration and current trials
- Spiral ganglion degeneration after deafness
- Neurotrophin-3 and functional recovery
- Delivery options for neurotrophic factors
- Nanoparticles and hydrogels as delivery vehicles
- Magnetic nanoparticle targeting
- Cell transplantation to the inner ear
- Embryonic transplantation and connexin 30 deficiency
- Autologous versus allogeneic cell sources
- Mesenchymal stromal cells and the secretome
- Extracellular vesicles as next-generation cell therapy
Summary
- Established practice today
- Principal limitations of middle ear delivery
- Instrumentation needed for future delivery
- Direction of travel for inner ear therapeutics
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- Haynes-Glasscock-Shambaugh Surgery of the Ear, Seventh Edition
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