COCHLEAR IMPLANT WITH MULTI-LAYER ELECTRODE

Abstract

A cochlear hearing aid system for providing electrical stimulation to auditory nerve fibers of a cochlea of a recipient of the cochlear hearing aid system is disclosed. The cochlear hearing aid system comprises a microphone configured to receive an acoustical signal and provide an audio signal based on the acoustical signal; a signal processor unit configured to receive the audio signal and process the audio signal; an electrode lead including a plurality of electrodes configured to stimulate the auditory nerve fibers based on the processed audio signal, wherein the electrode lead comprises: an electrode carrier maintaining the electrode contacts and wires, wherein the electrode carrier is made of silicone and is loaded by dexamethasone; a first layer (or sub-layers) of gelatin which is coated and chemically cross-linked selectively on a silicone outer surface of the electrode lead, wherein dexamethasone sodium phosphate is embedded in the first layer (or sub-layers); and a second layer of gelatin which is coated and physically cross-linked onto the first layer.

Claims

1. A cochlear hearing aid system for providing electrical stimulation to auditory nerve fibers of a cochlea of a recipient of the cochlear hearing aid system, the cochlear hearing aid system comprising: a microphone configured to receive an acoustical signal and provide an audio signal based on the acoustical signal; a signal processor unit configured to receive the audio signal and process the audio signal; an electrode lead including a plurality of electrodes configured to stimulate the auditory nerve fibers based on the processed audio signal, wherein the electrode lead comprises: an electrode carrier maintaining the electrode contacts and wires, wherein the electrode carrier is made of silicone and is loaded by dexamethasone; a first layer of gelatin which is coated and chemically cross-linked selectively on a silicone outer surface of the electrode lead, wherein dexamethasone sodium phosphate is embedded in the first layer; and a second layer of gelatin which is coated and physically cross-linked onto the first layer.

2. The cochlear hearing aid system according to claim 1, wherein several layers of gelatin are coated and cross-linked in order to reach a thicker first layer.

3. The cochlear hearing aid system according to claim 1, wherein several layers of gelatin are coated and chemically/covalently cross-linked in order to reach a thicker total layer.

4. The cochlear hearing aid system according to claim 1, wherein the first layer has a thickness of between 200 nm and 5 .Math.m and/or is composed of a single layer or multiple layers.

5. The cochlear hearing aid system according to claim 1, wherein some layers include a release drug solution.

6. The cochlear hearing aid system according to claim 5, wherein the release drug solution used for electrode preparation includes Dexamethasone Sodium Phosphate having a concentration of between 0.1 mg/mL and 100 mg/mL (saturated solution).

7. The cochlear hearing aid system according to claim 6, wherein a released Dexamethasone Sodium Phosphate concentration is between 0.1 and 175 .Math.g in 70 .Math.L of artificial perilymph.

8. The cochlear hearing aid system according to claim 5, wherein the drug is released in a chosen duration of between 10 minutes and 1 day, depending on the coating characteristics, in particular concentration, thickness and cross-linking.

9. A method for delivering a substance into a cochlea of a recipient of a cochlear hearing aid system, the method comprising: applying a first layer at least partially onto an outer surface of an electrode lead of the cochlear hearing aid system, wherein the first layer includes a gelatin substance; coating a second layer onto the first layer, wherein the second layer includes a gelatin substance; and inserting the electrode lead into the cochlea of the recipient.

10. The method according to claim 9, further comprising applying a release drug solution into or onto the first layer.

11. The method according to claim 9, wherein the first layer includes both the gelatin substance and a coupling agent, in particular EDC-NHS.

12. The method according to claim 1, wherein the substance is coupled to stem cells targeting hair cells or neurons.

13. The method according to claim 1, wherein the substance is coupled to Nerve Growth Factor (NGF).

14. The method according to claim 1, wherein applying the first layer comprises: dip-coating the electrode lead into a liquid, the liquid comprising the gelatin substance or the gelatin substance and a coupling agent; heating the electrode lead at a temperature between 30° C. and 45° C.; cleaning the electrode lead with water having a temperature of between 45° C. and 65° C.; and drying the electrode lead and cooling the electrode lead at below 0° C.

15. The method according to claim 14, wherein the release drug solution is applied into the liquid.

16. The method according to claim 10, wherein the release drug solution is applied into or onto the first layer by: dip-coating the electrode lead with the first layer into a liquid comprising the release drug solution for a period of between 12 hours and 48 hours or until the first layer has a swelling ratio of between 1.5 and 1.7; and drying the electrode lead.

17. The method according to claim 16, wherein the swelling ratio is determined as being the relation between the dry thickness in air of the layer and the swollen thickness in liquid of the layer.

18. The cochlear hearing aid system according to claim 2, wherein several layers of gelatin are coated and chemically/covalently cross-linked in order to reach a thicker total layer.

19. The cochlear hearing aid system according to claim 2, wherein the first layer has a thickness of between 200 nm and 5 .Math.m and/or is composed of a single layer or multiple layers.

20. The cochlear hearing aid system according to claim 3, wherein the first layer has a thickness of between 200 nm and 5 .Math.m and/or is composed of a single layer or multiple layers.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0043] The aspects of the disclosure may be best understood from the following detailed description taken in conjunction with the accompanying figures. The figures are schematic and simplified for clarity, and they just show details to improve the understanding of the claims, while other details are left out. Throughout, the same reference numerals are used for identical or corresponding parts. The individual features of each aspect may each be combined with any or all features of the other aspects. These and other aspects, features and/or technical effect will be apparent from and elucidated with reference to the illustrations described hereinafter in which:

[0044] FIG. 1 schematically illustrates a multi-layer electrode lead according to an exemplary embodiment;

[0045] FIG. 2 schematically illustrates applying a drug solution to a gelatin coated electrode carrier;

[0046] FIG. 3 shows an insertion force of an electrode lead when inserted into a synthetic cochlea as a function of a course standard;

[0047] FIG. 4A schematically shows an amount of released drug as a function of time for a silicone electrode loaded with 10% dexamethasone;

[0048] FIG. 4B schematically shows an amount of released drug as a function of time for a silicone electrode loaded with 10% dexamethasone and for a pure silicone electrode with a dexamethasone-loaded gelatin coating;

[0049] FIG. 5A schematically illustrates gelatin coating a PDMS fiber;

[0050] FIG. 5B schematically illustrates a first and a second step of gelatin coating a PDMS fiber;

[0051] FIG. 6 schematically illustrates some sub-steps of the first step of gelatin coating a PDMS fiber;

[0052] FIG. 7A schematically shows some sub-steps of the second step of gelatin coating a PDMS fiber;

[0053] FIG. 7B schematically illustrates some details of some sub-steps of the second step of gelatin coating a PDMS fiber;

[0054] FIG. 7C schematically illustrates some details of some sub-steps of the second step of gelatin coating a PDMS fiber;

[0055] FIG. 8A schematically illustrates gelatin coating a PDMS fiber cycle by cycle;

[0056] FIG. 8B schematically illustrates gelatin coating a PDMS fiber with one cycle and varying immersion time;

[0057] FIG. 9 schematically illustrates degradation of a gelatin coating;

[0058] FIG. 10 schematically illustrates encapsulating dexamethasone sodium phosphate in a gelatin coating;

[0059] FIG. 11 schematically shows the structural formula of dexamethasone sodium phosphate;

[0060] FIG. 12A schematically illustrates a first way of encapsulating dexamethasone sodium phosphate in a gelatin coating;

[0061] FIG. 12B schematically illustrates a second way of encapsulating dexamethasone sodium phosphate in a gelatin coating;

[0062] FIG. 13 schematically illustrates incorporation and release of dexamethasone sodium phosphate for a gelatin coated fiber;

[0063] FIG. 14 schematically illustrates release of dexamethasone sodium phosphate from a gelatin coating;

[0064] FIG. 15A schematically shows an absorbance curve of ultraviolet (UV) light as a function of the UV light wavelength;

[0065] FIG. 15B schematically shows a dexamethasone sodium phosphate calibration curve in ultraviolet (UV) visible spectroscopy at a wavelength of 242 nm; and

[0066] FIG. 16 schematically illustrates determining a release kinetic of a dexamethasone sodium phosphate-incorporated gelatin coating.

DETAILED DESCRIPTION

[0067] The detailed description set forth below in connection with the appended drawings is intended as a description of various configurations. The detailed description includes specific details for the purpose of providing a thorough understanding of various concepts. However, it will be apparent to those skilled in the art that these concepts may be practiced without these specific details. Several aspects of the apparatus and methods are described by various blocks, functional units, modules, components, circuits, steps, processes, algorithms, etc. (collectively referred to as “elements”). Depending upon particular application, design constraints or other reasons, these elements may be implemented using electronic hardware, computer program, or any combination thereof.

[0068] The electronic hardware may include micro-electronic-mechanical systems (MEMS), integrated circuits (e.g. application specific), microprocessors, microcontrollers, digital signal processors (DSPs), field programmable gate arrays (FPGAs), programmable logic devices (PLDs), gated logic, discrete hardware circuits, printed circuit boards (PCB) (e.g. flexible PCBs), and other suitable hardware configured to perform the various functionality described throughout this disclosure, e.g. sensors, e.g. for sensing and/or registering physical properties of the environment, the device, the user, etc. Computer program shall be construed broadly to mean instructions, instruction sets, code, code segments, program code, programs, subprograms, software modules, applications, software applications, software packages, routines, subroutines, objects, executables, threads of execution, procedures, functions, etc., whether referred to as software, firmware, middleware, microcode, hardware description language, or otherwise.

[0069] A hearing device (or hearing instrument, hearing assistance device) may be or include a hearing aid that is adapted to improve or augment the hearing capability of a user by receiving an acoustic signal from a user’s surroundings, generating a corresponding audio signal, possibly modifying the audio signal and providing the possibly modified audio signal as an audible signal to at least one of the user’s ears. ‘Improving or augmenting the hearing capability of a user’ may include compensating for an individual user’s specific hearing loss. The “hearing device” may further refer to a device such as a hearable, an earphone or a headset adapted to receive an audio signal electronically, possibly modifying the audio signal and providing the possibly modified audio signals as an audible signal to at least one of the user’s ears. Such audible signals may be provided in the form of an acoustic signal radiated into the user’s outer ear, or an acoustic signal transferred as mechanical vibrations to the user’s inner ears through bone structure of the user’s head and/or through parts of the middle ear of the user or electric signals transferred directly or indirectly to the cochlear nerve and/or to the auditory cortex of the user.

[0070] A “hearing system” refers to a system comprising one or two hearing devices, and a “binaural hearing system” or a bimodal hearing system refers to a system comprising two hearing devices where the devices are adapted to cooperatively provide audible signals to both of the user’s ears either by acoustic stimulation only, acoustic and mechanical stimulation, mechanical stimulation only, acoustic and electrical stimulation, mechanical and electrical stimulation or only electrical stimulation. The hearing system, the binaural hearing system or the bimodal hearing system may further include one or more auxiliary device(s) that communicates with at least one hearing device, the auxiliary device affecting the operation of the hearing devices and/or benefitting from the functioning of the hearing devices. A wired or wireless communication link between the at least one hearing device and the auxiliary device is established that allows for exchanging information (e.g. control and status signals, possibly audio signals) between the at least one hearing device and the auxiliary device. Such auxiliary devices may include at least one of a remote control, a remote microphone, an audio gateway device, a wireless communication device, e.g. a mobile phone (such as a smartphone) or a tablet or another device, e.g. comprising a graphical interface, a public-address system, a car audio system or a music player, or a combination thereof. The audio gateway may be adapted to receive a multitude of audio signals such as from an entertainment device like a TV or a music player, a telephone apparatus like a mobile telephone or a computer, e.g. a PC. The auxiliary device may further be adapted to (e.g. allow a user to) select and/or combine an appropriate one of the received audio signals (or combination of signals) for transmission to the at least one hearing device. The remote control is adapted to control functionality and/or operation of the at least one hearing device. The function of the remote control may be implemented in a smartphone or other (e.g. portable) electronic device, the smartphone / electronic device possibly running an application (APP) that controls functionality of the at least one hearing device.

[0071] In general, a hearing device includes i) an input unit such as a microphone for receiving an acoustic signal from a user’s surroundings and providing a corresponding input audio signal, and/or ii) a receiving unit for electronically receiving an input audio signal. The hearing device further includes a signal processing unit for processing the input audio signal and an output unit for providing an audible signal to the user in dependence on the processed audio signal.

[0072] The input unit may include multiple input microphones, e.g. for providing direction-dependent audio signal processing. Such directional microphone system is adapted to (relatively) enhance a target acoustic source among a multitude of acoustic sources in the user’s environment and/or to attenuate other sources (e.g. noise). In one aspect, the directional system is adapted to detect (such as adaptively detect) from which direction a particular part of the microphone signal originates. This may be achieved by using conventionally known methods. The signal processing unit may include an amplifier that is adapted to apply a frequency dependent gain to the input audio signal. The signal processing unit may further be adapted to provide other relevant functionality such as compression, noise reduction, etc. The output unit may include an output transducer such as a loudspeaker/ receiver for providing an air-borne acoustic signal to the ear of the user, a mechanical stimulation applied transcutaneously or percutaneously to the skull bone, an electrical stimulation applied to auditory nerve fibers of a cochlea of the user. In some hearing devices, the output unit may include one or more output electrodes for providing the electrical stimulations such as in a Cochlear Implant, or the output unit may include one or more vibrators for providing the mechanical stimulation to the skull bone.

[0073] A Cochlear Implant typically includes i) an external part for picking up and processing sound from the environment, and for determining sequences of pulses for stimulation of the electrodes in dependence on the sound from the environment, ii) a (typically wireless, e.g. inductive) transcutaneous communication link for transmitting information about the stimulation sequences and/or for transferring energy to iii) an implanted part allowing the stimulation to be generated and applied to a number of electrodes, which are implantable in different locations of the cochlea allowing a stimulation of different frequencies of the audible range. Such systems are e.g. described in US 4,207,441 and in US 4,532,930.

[0074] In an aspect, the hearing device comprises multi-electrode array e.g. in the form of a carrier comprising a multitude of electrodes adapted for being located in the cochlea in proximity of an auditory nerve of the user. The carrier is preferably made of a flexible material to allow proper positioning of the electrodes in the cochlea such that the electrodes may be inserted in cochlea of a recipient. Preferably, the individual electrodes are spatially distributed along the length of the carrier to provide a corresponding spatial distribution along the cochlear nerve in cochlea when the carrier is inserted in cochlea.

[0075] FIG. 1 illustrates a multi-layer electrode lead 100, e.g. comprised by a cochlear hearing aid system (not shown). Electrode lead 100 comprises an electrode carrier 110, a chemical gelatin layer 120 (an example of the first layer) and a physical gelatin layer 130 (an example of the second layer). Chemical gelatin layer 120a, 120b, 120c may consist of one or more sub-layers, e.g. two, three or N sub-layers, and/or have different thicknesses, e.g. a thickness of 2.5 .Math.m (e.g. for one sub-layer), 5 .Math.m (e.g. for two sub-layers) or N*2.5 .Math.m (e.g. for N sub-layers), with N being an arbitrary positive integer. In this way, a desired final thickness of the coating can be achieved. In a step 1, the electrode carrier 110 coated with the chemical gelatin layer 120a, 120b, 120c is additionally coated with the physical gelatin layer 130 which is disposed on and encloses the chemical gelatin layer 120. Such a double-layer coating of electrode carrier 110 is particularly advantageous for controlling an amount of drug released from the first layer 120. Further, chemical gelatin layer 120 offers a strong attachment of the gelatin coating on a silicone surface of the electrode carrier 110 by providing covalent (or ionic) bonding. A “base” thickness of 2.5 .Math.m is advantageous in that such a thickness may typically be well-controlled when coating the electrode carrier 110. The second layer (physical gelatin layer 130) offers high lubricity, thereby reducing a possible cochlear trauma when inserting electrode lead 100 into a recipient’s cochlea.

[0076] FIG. 2 illustrates applying a drug solution 200a, 200b (an example of the release drug solution) to a gelatin coated electrode carrier 110. Specifically, electrode carrier 110 is coated with a chemical gelatin layer 120. In steps 2, 4, the gelatin coated electrode carrier 110 is dipped into the drug solution 200a, 200b. Drug solution 200a, 200b is a solution, e.g. an aqueous solution, containing dexamethasone sodium phosphate (DSP). While drug solution 200a is a saturated solution with a concentration of 100 mg/ml, drug solution 200b has a concentration of 1 mg/ml. It is to be understood that any concentration in between these two values, such as 10 mg/ml, 20 mg/ml, 30 mg/ml, is also disclosed herewith. When dipped into the drug solution 200a, 200b, chemical gelatin layer 120 (i.e. the coating of electrode carrier 110) swells and the drug, i.e. DSP, is trapped in the chemical gelatin layer 120 (an example of the dexamethasone sodium phosphate being embedded in the first layer). On the other hand, DSP is also deposited on a surface of chemical gelatin layer 120 (a further example of the dexamethasone sodium phosphate being embedded in the first layer). After sufficiently swelling chemical gelatin layer 120, as indicated by steps 3, 5, the gelatin coated electrode carrier 110 is removed from the drug solution 200a, 200b. An amount of drug, i.e. DSP, potentially released from chemical gelatin layer 120′ depends on the concentration of the drug solution 200a, 200b and amounts, e.g., to 175 .Math.g in 70 .Math.l of perilymph for the saturated drug solution 200a and to 3 .Math.g in 70 .Math.l of perilymph for drug solution 200b. In other words, an amount of drug loaded into/onto chemical gelatin layer 120 may advantageously be controlled by means of the concentration of the drug solution 200a, 200b.

[0077] FIG. 3 shows an insertion force of an electrode lead when inserted into a synthetic cochlea as a function of a course standard. Thereby, the insertion force induced by an electrode lead, e.g. an electrode array, without any coating is shown as the black line, and the insertion force induced by an electrode lead with a first chemical gel coating (an example of the first layer) and a second physical gel coating (an example of the second layer) is shown as the grey line. The course standard may be understood as a proxy of the depth of penetration, i.e. depth of insertion, of the electrode lead into the cochlea. As can be seen in FIG. 3, the final maximum insertion force is reduced by 30% such that a possible cochlear trauma when inserting the electrode lead into a recipient’s cochlea is mitigated.

[0078] FIG. 4A shows an amount of released drug (in .Math.g) as a function of time (in days) for a silicone electrode loaded with 10% dexamethasone. To give some background, dexamethasone crystals may be mixed with silicone and when a device containing the silicone (e.g. the silicone electrode) gets in contact with body liquid, e.g. perilymph, the dexamethasone crystals dissolve and cause an anti-inflammatory effect on surrounding cells. As shown in FIG. 4A, an amount of drug, i.e. dexamethasone released as a function of time is approximately between 0 and 110 .Math.g during a time period of between 0 and 500 days (an example of a long-term drug release). While the solid black line indicates a prediction of the released drug as a function of time, the squares, triangles, crosses and stars indicate different measurements.

[0079] FIG. 4B shows an amount of released drug (in .Math.g) as a function of time (in days) for a silicone electrode loaded with 10% dexamethasone and for a pure silicone electrode with a dexamethasone-loaded gel coating. Thereby, curve 61 indicates a threshold of 3 .Math.g dexamethasone. As already described with reference to FIG. 4A, while the dexamethasone-loaded silicone electrode provides long-term drug release (cf. curve 62), a dexamethasone-loaded gel coating provides short-term drug release (cf. curve 63). Thus, FIG. 4B shows that a silicone electrode loaded with 10% dexamethasone (an example of the electrode carrier being made of silicone and being loaded by dexamethasone) and additionally coated with a dexamethasone-loaded gel coating (an example of a first layer in which dexamethasone sodium phosphate is embedded) allows to achieve a superposition of an increased or peak short-term drug release, e.g. over several hours, and a subsequent long-term drug release, e.g. over several years. As indicated by arrow 6, a peak of the short-term drug release may be modulated.

[0080] FIG. 5A illustrates gelatin coating (an example of applying a first layer) a PDMS (Polydimethylsiloxane) fiber 110 (an example of the electrode carrier) with a gelatin layer 120 (an example of the first layer), step 7.

[0081] FIG. 5B schematically illustrates a first step 8 and a second step 9 of gelatin coating the PDMS fiber 110. In the first step 8, the PDMS fiber 110 including a plurality of CH.sub.3 groups undergoes silanization, i.e. is covered with APTES (3-Aminopropyl)triethoxysilane), thereafter including a plurality of NH.sub.2 groups, as shown. In the second step 9, the PDMS fiber 110 including the plurality of NH.sub.2 groups is then chemically cross-linked and grafted with gelatin and EDC-NHS (an example of the coupling agent). Thus, after steps 8 and 9, the PDMS fiber 110 is coated with a gelatin layer 120 including gelatin and EDC-NHS (an example of the first layer including both the gelatin substance and a coupling agent).

[0082] FIG. 6 illustrates some sub-steps 11, 12, 13 of the first step 8 of gelatin coating the PDMS fiber 110. As indicated by sub-step 11, the PDMS fiber 110 includes a plurality of CH.sub.3 groups. As indicated by sub-step 12, the PDMS fiber 110 then undergoes a low-pressure plasma-system treatment, thereafter including a plurality of OH groups instead of the CH.sub.3 groups. Then, as indicated by sub-step 13, the actual silanization as described with reference to FIG. 5B is performed, e.g. in a reactor, after which the PDMS fiber 110 includes a plurality of NH.sub.2 groups, as shown.

[0083] FIG. 7A shows a process 1000 comprising some sub-steps 1100, 1200, 1300, 1400, 1500, 1600 of the second step 9 of gelatin coating a PDMS fiber. FIGS. 7B and 7C show some details of some sub-steps of the second step of gelatin coating a PDMS fiber.

[0084] Sub-step 1100 comprises B(-type) gelatin solubilization at 55° C. overnight and EDC-NHS coupling agent addition, whereby an amount of EDC-NHS in the gelatin solution is approximately 20 mM (millimolar, i.e. 0.001 mol/l). Thereby, the coupling agent EDC-NHS is added for grafting and chemical cross-linking the gelatin with the PDMS fiber. In detail, as illustrated in FIG. 7B, a (B-)gelatin solution 300 having a gelatin concentration of, e.g. 10 wt%, and having a temperature of about 55° C. is provided in a jar 35. Then, as indicated by arrow 14, the coupling agent EDC-NHS is added to the gelatin solution 300 such that the gelatin-EDC-NHS solution 400 comprises both the gelatin and the EDC-NHS.

[0085] Sub-step 1200 comprises dip-coating the PDMS fiber (an example of dip-coating the electrode lead into a liquid). In detail, as illustrated in FIG. 7C, the PDMS fiber 110 is immersed into the solution 400 (an example of the liquid comprising the gelatin substance and a coupling agent), step 15, is left immersed in the solution 400 for a predetermined amount of time and is then withdrawn from the solution 400, step 16. After withdrawal, the PDMS fiber 110 is coated with a gelatin layer 120. Thereby, a speed of immersing the PDMS fiber 110 into the solution 400 may amount to about, in particular exactly, 10 mm/s and a speed of withdrawing the PDMS fiber 110 from the solution 400 may amount to about, in particular exactly, 5 mm/s. A time, for which the PDMS fiber 110 is left immersed in the solution 400 (i.e. a dwell time) is variable, e.g. in the range of seconds to minutes. A time, during which the PDMS fiber dries amounts to about, in particular exactly, 5 s.

[0086] After the dip-coating, the coated PDMS fiber 110 is heated at 37° C. during 3 hours, sub-step 1300 (an example for heating the electrode lead at a temperature between 30° C. and 45° C.), washed with hot water having a temperature of about, in particular exactly, 55° C. in an ultra-sonic bath, sub-step 1400 (an example of cleaning the electrode lead with water having a temperature of between 45° C. and 65° C.), dried with liquid nitrogen, sub-step 1500 (an example of drying the electrode lead and cooling the electrode lead at below 0° C.), and stored in a Petri box in a fridge, sub-step 1600.

[0087] FIG. 8A illustrates gelatin coating a PDMS fiber 110 cycle by cycle. In steps 17, 18, a PDMS fiber 110 already coated with a gelatin layer 120, 121, e.g. as described above, is coated with two further gelatin layers 123, 125, e.g. as described above. Such a coating cycle by cycle provides the advantage of an improved reproducibility and control of a thickness of the gelatin coating.

[0088] FIG. 8B illustrates gelatin coating a PDMS fiber 110 with one cycle and varying immersion time. In step 19, the PDMS fiber 110 is left in the jar 35 for a variable immersion time, thereby controlling a thickness of the resulting gelatin layer 120, as shown in the figure. Such a coating with only one cycle and a variable immersion time provides the advantage of a less complex coating process while still having high reproducibility and control of a thickness of the gelatin coating.

[0089] Both, coating cycle by cycle as well as coating with a variable immersion time have been tested for electrode leads comprising only silicone (embodiment 1), silicone with Pt (platinum) (embodiment 2), and for electrodes (embodiment 3).

[0090] For embodiment 1, i.e. for only-silicone fibers, a coating cycle by cycle has been performed and it has been found that for 1, 3, 4, and 10 cycles, respectively, a coating thickness of approximately 1.7 .Math.m, 5-6 .Math.m, 7 .Math.m and 17 .Math.m was achieved.

[0091] For embodiment 2, i.e. for silicone fibers with Pt, a coating with a variable immersion time of 10, 20, 30, 40, and 50 seconds, respectively, has been performed and it has been found that for an immersion (or dwell) time of 20 seconds at 60° C., a coating thickness of approximately 2.5 .Math.m was achieved.

[0092] For embodiment 3, i.e. for electrodes (which are harder to cut), a coating with an immersion (or dwell) time of 20 seconds has been performed and it has been found that for an immersion (or dwell) time of 20 seconds at 60° C., a coating thickness of approximately 2.5 .Math.m was achieved.

[0093] FIG. 9 illustrates degradation of a gelatin coating 120, 120″. In step 20, the gelatin coating is brought into contact with water having a temperature of 37° C., i.e. imitating water in human cells. As a result of getting into contact with the water, as shown, the gelatin coating 120, 120‴ degrades. In particular, it has been found that after two days in PBS (phosphate-buffered saline) the gelatin is totally destroyed, while for immersion in homemade PBS, the swollen gel remains in the pillbox.

[0094] FIG. 10 illustrates encapsulating dexamethasone sodium phosphate (DSP) 500 in a gelatin coating 120 (an example of applying a release drug solution into or onto the first layer). As shown, in a step 21, the DSP 500 is embedded into, absorbed, resorbed, soaked up and/or sucked up by the gelatin coating 120 such that the gelatin coating 120′ contains the DSP 500 after the step 21.

[0095] FIG. 11 shows the structural formula of dexamethasone sodium phosphate 500, the water soluble version of dexamethasone.

[0096] FIG. 12A illustrates a first way of encapsulating dexamethasone sodium phosphate 500 in a gelatin coating 120. First, the DSP 500 and the EDC-NHS coupling agent 600 are added to a gelatin solution 300, as shown in the figure (an example of the release drug solution being applied into the liquid). Then, in step 22, the PDMS fiber 110 is dip-coated (see description above for details of the dip-coating) into the gelatin solution including the DSP 500 and the EDC-NHS coupling agent 600 and then washed with cold water. As a result, the gelatin coating 120′ contains the DSP 500. In other words, a first way of encapsulating the DSP 500 in a gelatin coating 120 comprises incorporation of the DSP 500 before the washing.

[0097] FIG. 12B illustrates a second way of encapsulating dexamethasone sodium phosphate 500 in a gelatin coating 120. Thereby, the already coated PDMS fiber 110 is immersed in an, e.g. aqueous, DSP solution 200 containing DSP 500 comprised by ajar 35, step 23 (an example of dip-coating the electrode lead with the first layer into a liquid comprising the release drug solution). The gelatin coating 120 swells and absorbs, resorbs, soaks up and/or sucks up the DSP 500 such that the swollen gelatin coating 120′ contains the DSP 500. In other words, a second way of encapsulating the DSP 500 in a gelatin coating 120 comprises incorporation of the DSP 500 after the washing.

[0098] Swelling properties of gelatin have been tested for various conditions. In particular, the gelatin has been immersed in liquid nitrogen and the resulting swelling ratio has been measured. In the particular measurement, a swelling ratio (defined as a size of the swollen gelatin layer divided by a size of the dried gelatin layer) was found to amount to 1.63 without a treatment and to 1.62 with a liquid nitrogen treatment. Thus, in other words, treatment with liquid nitrogen appears to have no effect on the swelling ratio.

[0099] FIG. 13 illustrates incorporation and release of dexamethasone sodium phosphate for a gelatin coated fiber. First, a 0.5 ml PCR tube 36 is filled with an, in particular aqueous, DSP solution 200, step 24. Then, a coated fiber 110 is immersed in the DSP solution 200 in pieces, step 25. The coated fiber 110 is left in the DSP solution 200 for swelling and DSP incorporation, whereby a swelling time amounts to about, in particular exactly, 1 hour and is calculated as

[00001]$\text{Swelling time}\text{=}\frac{H^2}{D}=\frac{{\left({10}^{-6}\text{s}\right)}^2}{{10}^{-9}\text{s}-{\text{10}}^{-12}\text{s}}={10}^{-3}\text{s}-\text{1s}$

[0100] After the swelling time, the coated fiber 110 is withdrawn from the DSP solution 200, step 26. The PCR tube 36 is filled with 200 .Math.l of fresh water, step 27. Thereafter, the drug, i.e. DSP, is released by immersing the coated fiber 110 including the swollen gelatin coating 120 which in turn includes the DSP into the fresh water 700, step 28.

[0101] FIG. 14 illustrates release of dexamethasone sodium phosphate 500 from a gelatin coating 120′ coating a PDMS fiber 110. The coated fiber is immersed in water having a temperature of 37° C. in the dark, i.e. imitating water in human cells. The DSP 500 is released from the gelatin coating 120′ into the water, step 29, leading to a reduced concentration of DSP 500 in the gelatin coating 120″, as illustrated in the figure.

[0102] FIG. 15A shows an absorbance curve of ultraviolet (UV) light for DSP as a function of the UV light wavelength. As illustrated, the absorbance reaches a local maximum 71 at a wavelength of 242 nm. Thus, in other words, an absorbance of UV light by DSP is maximum at a wavelength of 242 nm such that wavelength advantageously allows to determine a presence of DSP.

[0103] FIG. 15B schematically shows a dexamethasone sodium phosphate calibration curve in ultraviolet (UV) visible spectroscopy at a wavelength of 242 nm. As illustrated, the absorbance of UV light having a wavelength of 242 nm depends approximately linearly on the concentration of DSP (in .Math.g/ml), whereby the absorbance (which amounts to between 0 and 1.2) may be approximated as 0.0313 times the concentration of DSP in ug/ml (which amounts to between 0 ug/ml and 30 .Math.g/ml). Thus, UV spectroscopy at a wavelength of 242 nm advantageously allows to quantify the DSP concentration between 1 ug/ml and 30 .Math.g/ml.

[0104] FIG. 16 illustrates determining a release kinetic of a dexamethasone sodium phosphate-incorporated gelatin coating. First, a 0.5 ml PCR tube 36 is filled with an, in particular aqueous, DSP solution 200 and a PDMS fiber 110 coated with a gelatin layer 120 is immersed in the DSP solution 200. After the swelling, the coated fiber is withdrawn from the DSP solution 200 and the gelatin layer 120′ contains DSP, step 30. The PCR tube 36 is filled with 200 .Math.l of fresh water and the PDMS fiber 110 coated with the gelatin layer 120 is immersed into fresh water 700, step 31. After about, in particular exactly, one day, the release of drug, i.e. of DSP, expected in the perilymph, is determined, step 32. The following relationship between the DSP concentration of the DSP solution 200 and the expected DSP concentration in the perilymph has been found:

TABLE-US-00001 DSP solution concentration DSP concentration in perilymph more than 100 mg/ml (saturated) 11 × 10.sup.3 .Math.g/ml (too high) 1 mg/ml 1.2 ± 0.3 .Math.g/ml (nitrogen drying) (close to 5 .Math.g/ml) 1 mg/ml 3.1 ± 0.1 .Math.g/ml (air drying) (close to 5 .Math.g/ml) 1 mg/ml 4.6 ± 0.9 .Math.g/ml (no drying) (close to 5 .Math.g/ml) 0.1 mg/ml 0 .Math.g/ml (no release)

[0105] As can be seen from the above table, by setting the concentration of DSP in the (mother) solution, the amount of drug loaded into the electrode coating can be set and/or controlled.

[0106] It is intended that the structural features of the devices described above, either in the detailed description and/or in the claims, may be combined with steps of the method, when appropriately substituted by a corresponding process.

[0107] As used, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well (i.e. to have the meaning “at least one”), unless expressly stated otherwise. It will be further understood that the terms “includes,” “comprises,” “including,” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. It will also be understood that when an element is referred to as being “connected” or “coupled” to another element, it can be directly connected or coupled to the other element, but an intervening element may also be present, unless expressly stated otherwise. Furthermore, “connected” or “coupled” as used herein may include wirelessly connected or coupled. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. The steps of any disclosed method are not limited to the exact order stated herein, unless expressly stated otherwise.

[0108] It should be appreciated that reference throughout this specification to “one embodiment” or “an embodiment” or “an aspect” or features included as “may” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Furthermore, the particular features, structures or characteristics may be combined as suitable in one or more embodiments of the disclosure. The previous description is provided to enable any person skilled in the art to practice the various aspects described herein. Various modifications to these aspects will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other aspects.

[0109] The claims are to be accorded the full scope consistent with the language of the claims, wherein reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more.

[0110] Accordingly, the scope should be judged in terms of the claims that follow.