Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery

Cell specific targeting is an emerging field in nanomedicine. Homing of the multifunctional nanoparticles (MFNPs) is achieved by the conjugation of targeting moieties on the nanoparticle surface. The inner ear is an attractive target for new drug delivery strategies as it is hard to access and hearing loss is a significant worldwide problem. In this work we investigated the utility of a Nerve Growth Factor-derived peptide (hNgf_EE) functionalized nanoparticles (NPs) to target cells of the inner ear. These functionalized NPs were introduced to organotypic explant cultures of the mouse inner ear and to PC-12 rat pheochromocytoma cells. The NPs did not show any signs of toxicity. Specific targeting and higher binding affinity to spiral ganglion neurons, Schwann cells and nerve fibers of the explant cultures were achieved through ligand mediated multivalent binding to tyrosine kinase receptors and to p75 neurotrophin receptors. Unspecific uptake of NPs was investigated using NPs conjugated with scrambled hNgf_EE peptide. Our results indicate a selective cochlear cell targeting by MFNPs, which may be a potential tool for cell specific drug and gene delivery to the inner ea

Protective effects of minocycline and MDL 28170 in gentamicin ototoxicity

Gentamicin side-effects on cochlear structures and function are well known, but not the detailed intracellular molecular mechanisms which lead to aminoglycoside induced ototoxicity. Hair cell death occurs by apoptosis, by the activation of enzymatic cascades known to be involved in the programmed cell death, or by the release of cytochrome-c from the damaged mitochondria. In this paper we have investigated the active role of minocycline, a second-generation tetracycline, and of MDL 28170, a selective calpain inhibitor, in the protection of hair cells from GM damage in in vitro organospecific cultures of the organ of Corti. We used cultures from neonatal (P3) rat cochlea, treated with different dosages of GM, alone, or with the two protector drugs. We have observed a dose-dependent OHC and IHC loss. The GM damage was reduced after treatment with both drugs. These results were also supported by the Disk Diffusion Susceptibility Test (Kirby-Bauer Method), in which we used drug treated organs of Corti. The data suggest that minocycline, previously reported to inhibit the release of cytochrome-c, and MDL 28170, prevent GM induced programmed cell death pathway in cochlear HC