Achievements

Our manufactuers have produced a diverse number of different nanoparticles, that have different sizes, chemistry and physical properties. These large number of nanoparticles provides the base for our in vitro and in vivo research.

Toxicity testing; The potential toxicity of NPs is assessed using appropriately developed test systems such that testing can eventually be carried out on tissues relevant for the inner ear. Ideally, benchmark NPs that can serve as negative and positive controls for cytotoxicity tests would be used as recommended by Oberdörster et al. 2005 some of which show characteristics not suitable for the test systems. However as neither EMEA nor NIH can provide recommendations to benchmark with the reference materials at this time, it was decided to use commercial NPs available on the market. For NP targeting the appropriate ligands have to identified and  developed, these efforts are well under way. This work uses a combination of manufacturing and molecular biological techniques with the major challenge of producing functional, biologically active molecules that have receptors on one side and their ligands on the other. With the ultimate aim of producing NPs with slective targeting of cells in the inner ear.

In vivo evaluation of NPs; we perform essential in vivo validation of in vitro screening information on NP distribution, targetability, cell uptake, biocompatibility, toxicity, bioefficacy and model membrane transit in appropriate animal models. Established inner ear disease models exist in the guinea pig, mouse and rat. Our new TEM experimental data indicates that the neural structures can be accessed by round window membrane delivery, as the cochlear fluid pathways will deliver the NPs to spiral ganglion cells through holes present in the bone.

MRI visualisation of NPs; We evaluate the visibility, distribution and targeting of NPs loaded with contrasting agents.