Dexamethasone-loaded cochlear implants: How to provide a desired “burst release”

Abstract

Cochlear implants containing iridium platinum electrodes are used to transmit electrical signals into the inner ear of patients suffering from severe or profound deafness without valuable benefit from conventional hearing aids. However, their placement is invasive and can cause trauma as well as local inflammation, harming remaining hair cells or other inner ear cells. As foreign bodies, the implants also induce fibrosis, resulting in a less efficient conduction of the electrical signals and, thus, potentially decreased system performance. To overcome these obstacles, dexamethasone has recently been embedded in this type of implants: into the silicone matrices separating the metal electrodes (to avoid short circuits). It has been shown that the resulting drug release can be controlled over several years. Importantly, the dexamethasone does not only act against the immediate consequences of trauma, inflammation and fibrosis, it can also be expected to be beneficial for remaining hair cells in the long term. However, the reported amounts of drug released at “early” time points (during the first days/weeks) are relatively low and the in vivo efficacy in animal models was reported to be non-optimal. The aim of this study was to increase the initial “burst release” from the implants, adding a freely water-soluble salt of a phosphate ester of dexamethasone. The idea was to facilitate water penetration into the highly hydrophobic system and, thus, to promote drug dissolution and diffusion. This approach was efficient: Adding up to 10% dexamethasone sodium phosphate to the silicone matrices substantially increased the resulting drug release rate at early time points. This can be expected to improve drug action and implant functionality. But at elevated dexamethasone sodium phosphate loadings device swelling became important. Since the cochlea is a tiny and sensitive organ, a potential increase in implant dimensions over time must be limited. Hence, a balance has to be found between drug release and implant swelling.

Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro

“…Among these, inflammation-suppressing substances, such as glucocorticoids, and especially dexamethasone, have been widely tested as a potential therapy to treat inner ear pathologies including sudden sensorineural hearing loss (SSNHL) [ 7 , 8 , 9 , 10 ], Menière’s disease [ 11 , 12 , 13 , 14 ], and acute tinnitus [ 15 ]. Additionally, dexamethasone is intensively investigated for its benefit in cochlear implant (CI) patients [ 16 ]. Today, for patients with a severe-to-profound SNHL or deafness, independently of age, CIs are the most effective treatment.…”

An Ultrasoft and Flexible PDMS-Based Balloon-Type Implantable Device for Controlled Drug Delivery

“…Such implants utilize drugs in powder form, where water infiltrates via a channel into the drug reservoir to dissolve the drug, and then the drug molecules could diffuse out for sustained drug release. In addition, these implantable devices are often associated with high initial burst release [ 13 , 14 ], affecting long-term efficacy and zero-order drug release [ 15 , 16 ], which limits their use for long-term drug delivery. Most reservoir-based implantable systems are manufactured via molding of various soft polymers integrated with a permeable membrane, making them relatively rigid and thick [ 11 , 17 , 18 ].…”

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

“…Glucocorticosteroids were intensively studied to reduce EIT and DEX-eluting electrodes, resulting in a considerable amount of research data [85][86][87][88][89][90]. In an animal model, Douchement et al used electrodes embedded in a silicone matrix loaded with various concentrations of DEX and compared them to simple electrodes, evaluating the hearing thresholds at 4-6 weeks after surgery and one year after surgery.…”