Achievements

The vast majority of patients suffering from hearing disorders, ranging from total deafness to age-related hearing loss, can hope to have their hearing restored through the insertion of 8 safe multifunctional nanoparticles into the inner ear. Eventually, a nano-hearing implant will also be developed within the next 10 years.

NANOEAR made a real breakthrough by obtaining a most innovative 3D imaging of the functioning human cochlea, or inner ear, by furnishing the nanoparticles with MRI visible (and EMEA-accepted) contrast agents, such as SPION and Gadolinium chelate. This allows the project's team to see where the nanoparticles target, accumulate and are secreted, in order to deliver corticosteroids, peptides, genes, siRNA and shRNA through the same route. The MRI of nanoparticles, thanks to its new properties, can also provide safer and more detailed imaging than the one obtained with traditional contrast agents.

The process works like this: the multifunctional nanoparticles target specific, selected regions in the inner ear. They are imaged through MRI and tracked up to the point where they deliver a payload of drugs, proteins or genes.   

The project’s team also demonstrated that the best access to the inner ear and balance organ is not through the round window membrane as it had been believed until now, but the most efficient drug delivery route is through the ligament around the small ossicule in the oval window. By visualizing the functioning cochlea in 3D, it is also possible for scientists to visualize hearing disorders that were previously unidentifiable.

Among NANOEAR’s technological achievements in drug delivery, key peptides were recently identified, which help the nanoparticles to escape the endosome system, where most of them are trapped and dysfunctionalized by the cells lysosomal enzymes. By escaping this system the nanoparticles can deliver the therapeutic agents that are aimed to work either in the cytoplasm or in the nucleus. The nanoparticles can also carry hydrophilic or hydrophobic drugs, growth factors, genes and mimetics (small drugs working as larger proteins).

A "stealth cover" allows the nanoparticles to pass the cell membranes, unrecognized by the immune system. The project team recently saw that the nanoparticles can be traced from the ear up to the entry of the central nervous system, as they prefer to pass along the nerves. Now the system should be fine-tuned by developing more advanced targeting moieties and organizing trials with commercial mimetics. The delivery of proteins, drugs and genes has been achieved in animal models.

Imaging and drug delivery are not the only remarkable achievements of the project. NANOEAR’s third frontier is a radically new cochlear implant, which is still under development and can be expected within the next 10 years. The principles of this new type of hearing aid and nerve stimulator based on nanotechnology, or “nano-hearing aid”, is still on drawing board and should be worked out in detail. It would be a major breakthrough. In fact, conventional technology is still not quite within the "nano-range"; in particular, the electronics and the coils are currently in the "micro-technology" class. (See the attached movie)

The cochlea implants can be coated with drugs with novel plasma coating technology providing 10-20 um layer consisting of nanoparticle carrier. The drug from the nanoparticle is dispersed by slow release mechanism. The other innovation is the incorporation of to nanogels into a tiny storage space within the cochlear implant electrode. From this storage the drug diffuses to fight surgical trauma and revitalize the inner ear. Notably, the electrode is as flexible and smooth as non-drug containing electrodes.

NANOEAR holds several patents, mainly in electrode technology and drug incorporation, and is aiming to produce prototypes for human use. It is in the process of establishing joint ventures with the pharmaceutical industry to commercialize the nanodelivery items and provide a much needed carrier system for the regenerative medicine industry.