Fine control of drug delivery for cochlear implant applications

Abstract

Cochlear implants are neuroprostheses that are inserted into the inner ear to directly electrically stimulate the auditory nerve, thus replacing lost cochlear receptors, the hair cells. The reduction of the gap between electrodes and nerve cells will contribute to technological solutions simultaneously increasing the frequency resolution, the sound quality and the amplification of the signal. Recent findings indicate that neurotrophins (NTs) such as brain derived neurotrophic factor (BDNF) stimulate the neurite outgrowth of auditory nerve cells by activating Trk receptors on the cellular surface (1–3). Furthermore, small-size TrkB receptor agonists such as di-hydroxyflavone (DHF) are now available, which activate the TrkB receptor with similar efficiency as BDNF, but are much more stable (4). Experimentally, such molecules are currently used to attract nerve cells towards, for example, the electrodes of cochlear implants. This paper analyses the scenarios of low dose aspects of controlled release of small-size Trk receptor agonists from the coated CI electrode array into the inner ear. The control must first ensure a sufficient dose for the onset of neurite growth. Secondly, a gradient in concentration needs to be maintained to allow directive growth of neurites through the perilymph-filled gap towards the electrodes of the implant. We used fluorescein as a test molecule for its molecular size similarity to DHF and investigated two different transport mechanisms of drug dispensing, which both have the potential to fulfil controlled low-throughput drug-deliverable requirements. The first is based on the release of aqueous fluorescein into water through well-defined 60-μm size holes arrays in a membrane by pure osmosis. The release was both simulated using the software COMSOL and observed experimentally. In the second approach, solid fluorescein crystals were encapsulated in a thin layer of parylene (PPX), hence creating random nanometer-sized pinholes. In this approach, the release occurred due to subsequent water diffusion through the pinholes, dissolution of the fluorescein and then release by out-diffusion. Surprisingly, the release rate of solid fluorescein through the nanoscopic scale holes was found to be in the same order of magnitude as for liquid fluorescein release through microscopic holes.

Cochlear Implant Strategies and Biomaterials from Past to Future

“…Optimization of the electrode nerve interface could be achieved by introducing drug substances into the cochlea which could cause the growth of neurites to the electrode [21,22].…”

Two are Better than One: Combining ZnO and MgF2 Nanoparticles Reduces Streptococcus pneumoniae and Staphylococcus aureus Biofilm Formation on Cochlear Implants

“…The CI-based platforms were created by coating a silicone substrate with a Parylene fi lm, which confers low water permeability and biocompatibility. [ 25 ] The Parylene fi lm had an average thickness of 1.2 µm and was created at the HES-SO University of Applied Sciences (Switzerland). Henceforth, "CI" will refer to the Parylene-silicone CI-based platform and "coating" will refer to the NPs.…”

“…There was a 20% reduction in alamarBlue signal from HF cultured with uncoated CI fragments relative to the HF cultured in an empty microplate well (without any fragment in place). This could be explained by some adverse effects on cell viability from the Parylene layer (generally considered inert and biocompatible) [ 25 ] and/or a mechanical effect of the free-fl oating implant fragments. Alternatively, as the readings were performed with the fragment inside the wells, this phenomenon could also be an effect of shadowing.…”

“…[ 25 ] Silicone used alone as a layer on the implant provides biocompatibility but allows water penetration; the latter may affect the electrical properties of the device such as the impedance. Adding a Parylene layer on the CI, although not a typical procedure, blocks water permeability into the device and can improve its functionality.…”

“…Adding a Parylene layer on the CI, although not a typical procedure, blocks water permeability into the device and can improve its functionality. [ 25 ] Henceforth, "CI" will refer to the Parylene-silicone CI-based platform, and "coating" will refer to the NPs. The sonochemical deposition was carried out by ultrasound-assisted irradiation of the precursor solution in the presence of the solid surface; this coating procedure is called in situ.…”