Abstract:
An implantable drug-doped component, e.g., a cochlear implant, includes host material, a host-embedded drug and a sacrificial material integrated with the host. Upon exposure of the sacrificial material to a solvent, e.g., perilymph fluid, voids in the host are created which facilitate release of the drug. The host can be, e.g., polysiloxane or silicone rubber. The sacrificial material, e.g., can be a glucose monomer, sugar, cyclodextrin, a salt, a bioresorbable material, hyaluronic acid, polyurethane, polyester, polyamide, polyvinyl alcohol, polyacrylic acid, etc. Alternatively, the sacrificial material can be the host, and can facilitate release of the drug through changing a property of the sacrificial material, e.g., by exposing the component to an ethanol wash. For a cochlear implant, e.g., the drug doped material can be applied to a non-stimulating surface of the electrode array.

Description:
FIELD 
       [0001]    The disclosed technology relates to implantable medical devices, and in particular to implantable medical devices used to deliver drugs. 
       BACKGROUND 
       [0002]    Implantable medical devices are capable of providing a wide range of benefits to a patient. Traditionally, there has been interest in delivering bioactive substances or chemicals (generally and collectively referred to herein as “drugs”) in conjunction with such medical devices for a variety of purposes. For example, in one conventional approach the implantable medical device is coated with a bioactive substance. In other conventional approaches various techniques for delivering drugs in liquid form to a target location in a patient from an external or implanted reservoir. 
         [0003]    In many conventional approaches, a bioactive substance is integrated into the polymeric coating of the implantable medical device or accompanying component. These and other conventional approaches typically require the incorporation of the drug into the implantable medical device during the manufacturing process of the device. This requirement introduces a number of difficult problems and challenges for the manufacturing and sterilization processes. On the other hand, the use of reservoirs provides significant limitations to many aspects of the administration of the drug therapy. 
       SUMMARY 
       [0004]    The technology includes an implantable drug-doped component, e.g., a cochlear implant, that includes a host material, a drug embedded in the host material, and a sacrificial material integrated with the host material. The sacrificial material facilitates the release of the embedded drug from the drug-doped component. The sacrificial material can facilitate the release of the drug from the drug-doped component through the creation of voids in the host material upon dissolution of the sacrificial material upon contact with a solvent. The contact with a solvent can be upon implant of the component in a recipient, e.g., perilymph as the solvent. The host material can be one or more of a polysiloxane and a silicone rubber. The drug can be one or more of an anti-inflammatory, a growth factor, an antibody, an anti-oxidant, an antibiotic, and a corticosteroid. The sacrificial material can be one or more of: a glucose monomer, a sugar, cyclodextrin, a material that is at least one of dissolvable and re-sorbable in the environment of an implant site, a salt, a bioresorbable material, hyaluronic acid, polyurethane, polyester, polyamide, polyvinyl alcohol, and polyacrylic acid. In some embodiments, the sacrificial material is the host material, and the sacrificial material facilitates the release of the drug from the drug-doped component through changing a property of the sacrificial material. The change in property can be brought about by exposing the drug-doped component to an ethanol wash. For a cochlear implant comprising a drug-doped component, the drug doped material can be applied to a non-stimulating surface of the electrode array of the cochlear implant. The drug doped material can be a physical feature of the stimulating medical device, such as a soft tip, a ridge, or a spine. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0005]    Embodiments of the disclosed technology are described below with reference to the attached drawings, in which: 
           [0006]      FIG. 1  is a perspective view of an exemplary stimulating medical device, a cochlear implant, having an electrode assembly in accordance with embodiments of the present technology; 
           [0007]      FIG. 2  is a side view of a conventional implantable component of a cochlear implant; 
           [0008]      FIG. 3  is a side view and a cross section view of a section of an electrode assembly; 
           [0009]      FIG. 4  is a schematic representation of a set of relationships between a carrier member, a drug, and a sacrificial material in accordance with embodiments of the present technology; 
           [0010]      FIG. 5  is a schematic representation of a set of relationships between a carrier member, a drug, and a sacrificial material in accordance with embodiments of the present technology; 
           [0011]      FIG. 6  is a flowchart of methods in accordance with embodiments of the present technology; 
           [0012]      FIG. 7A  is a view of a section of an electrode assembly with drug-doped material extending down the lateral non-stimulating surface of the carrier member, in accordance with embodiments of the present technology; and 
           [0013]      FIG. 7B  illustrates exemplary cross sections of a spine of  FIG. 7A , in accordance with embodiments of the present technology. 
       
    
    
     DETAILED DESCRIPTION 
       [0014]    Embodiments are described herein primarily in connection with one type of implantable medical device, a hearing prosthesis, and more specifically a cochlear implant. Cochlear implants are hearing prostheses that deliver electrical stimulation, alone or in combination with other types of stimulation, to the cochlear of a recipient. Therefore, as used herein a cochlear implant refers to a device that delivers electrical stimulation in combination with other types of stimulation, such as acoustic and/or mechanical stimulation. 
         [0015]    It would be appreciated that embodiments of the present technology can be implemented in any cochlear implant or other hearing prosthesis now know or later developed; including auditory brain stimulators (also known as auditory brainstem implants (ABIs)). Furthermore, it would be understood that embodiments of the present technology can be implemented in implantable medical devices other than cochlear implants such as neurostimulators, cardiac pacemakers/defibrillators, functional electrical stimulators (FES), spinal cord stimulators (SCS), etc. 
         [0016]      FIG. 1  is a perspective view of an exemplary cochlear implant  100  implanted in a recipient having an outer ear  101 , a middle ear  105 , and an inner ear  107 . Components of outer ear  101 , middle ear  105 , and inner ear  107  are described below, followed by a description of cochlear implant  100 . 
         [0017]    In a fully functional ear, outer ear  101  comprises an auricle  110  and an ear canal  102 . An acoustic pressure or sound wave  103  is collected by auricle  110  and channeled into and through ear canal  102 . Disposed across the distal end of ear cannel  102  is a tympanic membrane  104  that vibrates in response to sound wave  103 . This vibration is coupled to oval window or fenestra ovalis  112  through three bones of middle ear  105 , collectively referred to as the ossicles  106  and comprising the malleus  108 , the incus  109 , and the stapes  111 . Bones  108 ,  109 , and  111  of middle ear  105  serve to filter and amplify sound wave  103 , causing oval window  112  to articulate, or vibrate, in response to vibration of tympanic membrane  104 . This vibration sets up waves of fluid motion of the perilymph within cochlea  140 . Such fluid motion, in turn, activates tiny hair cells (not shown) inside of cochlea  140 . Activation of the hair cells causes appropriate nerve impulses to be generated and transferred through the spiral ganglion cells (not shown) and auditory nerve  114  to the brain (also not shown) where they are perceived as sound. 
         [0018]    Cochlear implant  100  comprises an external component  142  that is directly or indirectly attached to the body of the recipient, and an internal or implantable component  144  that is temporarily or permanently implanted in the recipient. External component  142  typically comprises one or more sound input elements, such as microphone  124  for detecting sound, a sound processing unit  126 , a power source (not shown), and an external transmitter unit  128 . External transmitter unit  128  comprises an external coil  130 , and preferably, a magnet (not shown) secured directly or indirectly to external coil  130 . Sound processing unit  126  processes the output of microphone  124  that is positioned, in the depicted embodiment, by auricle  110  of the recipient. Sound processing unit  126  generates encoded signals, sometimes referred to herein as encoded data signals, which are provided to external transmitter unit  128  via a cable (not shown). 
         [0019]    Internal component  144  comprises an internal receiver unit  132 , a stimulator unit  120 , and an elongate stimulating lead assembly  118 . Internal receiver unit  132  comprises an internal coil  136 , and preferably, a magnet (also not shown) fixed relative to the internal coil. Internal receiver unit  132  and stimulator unit  120  are hermetically sealed within a biocompatible housing, sometimes collectively referred to as a stimulator/receiver unit. Internal coil  136  receives power and stimulation data from external coil  130 , as noted above. Elongate stimulating lead assembly  118  has a proximal end connected to stimulator unit  120 , and extends through mastoid bone  119 . Lead assembly  118  has a distal region, referred to as electrode assembly  145 , implanted in cochlea  140 . As used herein the term “stimulating lead assembly,” refers to any device capable of providing stimulation to a recipient, such as, for example, electrical or optical stimulation. 
         [0020]    Electrode assembly  145  may be implanted at least in basal region  116  of cochlea  140 , and sometimes further. For example, electrode assembly  145  may extend towards apical end of cochlea  140 , referred to as cochlea apex  134 . Electrode assembly  145  may be inserted into cochlea  140  via a cochleostomy  122 , or through round window  121 , oval window  112 , and the promontory  123  or opening in an apical turn  147  of cochlea  140 . 
         [0021]    Electrode assembly  145  has disposed therein or thereon a longitudinally aligned and distally extending array  146  of electrode contacts  148 , sometimes referred to as electrode array  146  herein. Throughout this description, the term “electrode array” means a collection of two or more electrode contacts, sometimes referred to simply as contacts herein. As used herein, electrode contacts or other elements disposed in a carrier refer to elements integrated in, positioned on, or generally attached to the carrier member. As such, electrode array  146  is referred to herein as being disposed in electrode assembly  145 . Stimulator unit  120  generates stimulation signals which are applied by electrodes  148  to cochlea  140 , thereby stimulating auditory nerve  114 . 
         [0022]    In cochlear implant  100 , external coil  130  transmits electrical signals (i.e., power and stimulation data) to internal coil  136  via a radio frequency (RF) link. Internal coil  136  is typically a wire antenna coil comprised of multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire. The electrical insulation of internal coil  136  is provided by a flexible silicone molding (not shown). In use, implantable receiver unit  132  may be positioned in a recess of the temporal bone adjacent auricle  110  of the recipient. 
         [0023]    As noted,  FIG. 1  illustrates a context of the present technology in which cochlear implant  100  includes an external component  142 . It would be appreciated that in alternative embodiments, cochlear implant  100  comprises a totally implantable prosthesis that is capable of operating, at least for a period of time, without the need of an external component. In such embodiments, all components of cochlear implant  100  are implantable, and the cochlear implant operates in conjunction with external component  142 . 
         [0024]      FIG. 2  is a simplified side view of an embodiment of internal component  144 , referred to herein as internal component  244 . As shown in  FIG. 2 , internal component  244  comprises a stimulator/receiver unit  202 , which, as described above, receives encoded signals from an external component of the cochlear implant. Connected to stimulator/receiver unit  202  is a stimulating lead assembly  250 . Stimulating lead assembly  250  terminates in an electrode assembly  218  that comprises a proximal region  210  and an intra-cochlear region  212 . Intra-cochlear region  212  is configured to be implanted in the recipient&#39;s cochlea and has disposed thereon an array  246  of electrode contacts  248 . Proximal region  210  is configured to be positioned outside of the recipient&#39;s cochlea. 
         [0025]    In certain embodiments, electrode assembly  218  is configured to adopt a curved configuration during or after implantation into the recipient&#39;s cochlea. To achieve this, in certain embodiments, electrode assembly  218  is pre-curved to the same general curvature of a cochlea. In such embodiments, electrode assembly  218  is referred to as perimodiolar electrode assembly that is held straight by, for example, a stiffening stylet (not shown), which stylet is removed during implantation so that the electrode assembly may adopt its curved configuration when in the cochlea. Other methods of implantation, as well as other electrode assemblies that adopt a curved configuration, may be used in embodiments of the present technology. 
         [0026]    In other embodiments, electrode assembly  218  is a non-perimodiolar electrode assembly that does not adopt a curved configuration. For example, electrode assembly  218  may comprise a straight electrode assembly or a mid-scala assembly that assumes a mid-scala position during or following implantation. 
         [0027]    In the illustrative embodiments of  FIG. 2 , stimulating lead assembly  250  further comprises a helix region  204  and a transition region  206  connecting stimulator/receiver unit  202  to electrode assembly  218 . Helix region  204  prevents the connection between stimulator/receiver  202  and electrode assembly  218  from being damaged due to movement of internal component  244  which may occur, for example, during mastication. 
         [0028]    There have been a number of proposals for delivering drugs to an implant site. Successful delivery of drugs to an implant site can provide benefits such as: faster recovery at the implant trauma, an increase in stimulation effectiveness (e.g., by supporting hair cell survival and growth in cochlear implants), directly targeting diseases such as tinnitus, promoting acceptance of the implant at the site, and facilitating the function of the implant. Drug delivery to a cochlear implant site can be achieved, inter alia, through embedding a portion of the implant, e.g., the electrode assembly, with the drug. As used herein, the term “drug” includes, but is not limited to, therapeutic, prophylactic, and diagnostic agents. 
         [0029]    Many implants, e.g., cochlear implants, employ structural elements that are intended to remain in a recipient for the long term. As such, these structural elements are typically more hydrophobic than not, and are required to maintain structural integrity over the long term. For example, silicone rubber, typically used as a structural element in such devices, is hydrophobic in nature, and this is a significant impediment to complete drug release in the short term from a silicone rubber/drug mix. In particular, short-term (e.g., 29 days or less) drug delivery from devices intended to implanted for the long term has proved challenging. 
         [0030]    Embodiments of the present technology employ a sacrificial material with a drug, in combination with a host material (e.g., the carrier member  310  of the electrode assembly, or at least a portion of the outer layer of the receiver/stimulator unit) to form a drug doped material. Using the combination of the sacrificial material, drug, and host material can modify the characteristics of the aggregate material (e.g., the carrier member  310 ) and enhance drug bioavailability. 
         [0031]      FIG. 3  shows an end section of a typical electrode assembly  345  comprising an elongate electrode carrier member  310  having a plurality of electrode contacts  348  mounted thereon. This particular electrode assembly  345  defines a lumen  320  (shown in cross-section A-A) that, prior to insertion of the assembly  345  into the cochlea, can receive a substantially straight stylet. Such a stylet typically has a stiffness that is sufficient to retain the assembly  345  in a straight configuration. Other electrode assemblies may be used in embodiments of the present technology. Conductive pathways  330  are shown in the cross section of the electrode assembly  345 . Each conductive pathway  330  is typically connected to a contact  348 . 
         [0032]    The carrier member  310  is a structural element of the electrode assembly  345 , and is typically made from a hydrophobic material such as medical grade silicone. The carrier member  310  can be made from any number of polysiloxanes, for example, silicone rubber Med  4860  available from Nusil. 
         [0033]    Some embodiments of the technology are referred to herein as “void-creating” embodiments. 
         [0034]    Referring to  FIG. 4 , in some void-creating embodiments  400  of the technology, the drug  410  and a sacrificial material  420  are combined and added to the host material  430  of the carrier member  310 . Elution of the drug through the host material  430  is facilitated by voids in host material  430  created when the sacrificial material has been sacrificed, e.g., by exposure to one or more of a solvent, eluent, heat, or electromagnetic field. Voids decrease the time required for a sufficient proportion of the drug to enter the body surrounding the implant with less drug residue remaining in the electrode assembly, therefore increasing the amount of drug available for its intended purpose. 
         [0035]    In some void-creating embodiments, the sacrificial material can be a glucose monomer, or sugar, e.g., cyclodextrins, sometimes called cycloamyloses, that are produced from starch by means of enzymatic conversion. Such materials are used in food, pharmaceutical, and chemical industries, as well as agriculture and environmental engineering. The sacrificial material can be any number of natural or synthetic agents which dissolve or re-sorb, including but not limited to salts. The sacrificial material also can be a bioresorbable material such as hyaluronic acid, poly-vinyl alcohol (PVA), poly acrylic acid (PAA), polyurethanes, polyesters, polyamides among others. 
         [0036]    Referring to  FIG. 5 , in some void-creating embodiments  400  of the technology, the drug  430  can be coated in the sacrificial material  420  and elution can occur by the drug  430  leaving the host material  430  as the sacrificial material  420  dissolves. 
         [0037]    Without being bound by theory, it is believed that combining the drug with a sacrificial material in the largely hydrophobic carrier body allows the drug to elute through the carrier body in less time than it otherwise would based at least in part on voids created when the sacrificial material leaves the bulk material. 
         [0038]    In some embodiments of the technology, referred to herein as “wash” embodiments, the drug-doped material is exposed, e.g., via dipping or through a wash, to a substance that improves the drug doped material&#39;s ability to release the drug. Without being bound by theory, it is believed that washing a drug-doped component in a wash such as those described herein, allows the drug to elute through the drug-doped material in less time than it otherwise would, based on the wash breaking oligomers of the host material. 
         [0039]    In some wash embodiments of the technology, a drug-dope device (or at least the regions of the device carry the drug) is dipped in a wash, e.g., an ethanol wash, for a suitable period of time. This step can be performed during manufacturing, soon after manufacture of the device, or just prior to insertion of the device. 
         [0040]    In some embodiments of the technology, the area of drug application is limited. Limiting the area of application of the drug doped material can assist in maintaining the integrity of the carrier member  410  after release of the drug has taken place. It is likely that after release of the drug from the drug doped material, voids would be left within the bulk material of the carrier member. These voids could result in negative effects, for example, allow for an ionic path for fluids to access the conductive pathway insulation and joins of conducting pathways to stimulating contacts. The voids may also impact upon the bulk material acting as a retention mechanism for the stimulating contacts within the carrier member  410 . The voids could also cause delaminating of bulk material layers during a multiple molding processes. Limiting the area of application for the drug doped material would avoid these issues. 
         [0041]    Referring to  FIG. 7A , a section  700  of an electrode assembly with the drug-doped material extending down the lateral non-stimulating surface (surface  720 ) of the carrier member  710  away from the contacts  740 , for example, in the form of a spine  730 . The drug-doped material also may exist as a feature of the carrier member  710 , for example, in the form of a soft tip  750 , among others.  FIG. 7B  illustrates exemplary cross sections of such a spine  730   a,    730   b,    730   c,  and  730   d.    
         [0042]    The drug can be an anti-inflammatory such as Dexamethasone. Other drugs that could be applied using this technique could include growth factors, antibodies, anti-oxidants, anti-inflammatory, antibiotics, corticosteroid etc, as applicable. 
         [0043]    The technology includes methods of delivering a drug to an implant site. As an exemplary method, consider delivery of a drug to the implant site of a cochlear implant electrode assembly using any one of the devices described herein. In such method, as illustrated in  FIG. 6 , a cochleostomy is formed  610 . The device (as described above to contain the drug) is inserted through the cochleostomy  620 . The drug is one or both of allowed and caused to be released from the drug-doped electrode assembly  630 . Methods for allowing or causing the drug to be released from the drug-doped assembly containing sacrificial material include exposing the one or more of: a solvent or eluent such as perilymph fluid; heat (such as the recipient&#39;s body heat); an electromagnetic field; and a vibration, sonic, or ultrasound force. 
         [0044]    While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. It will be apparent to persons skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents. All patents and publications discussed herein are incorporated in their entirety by reference thereto.