ABSTRACT
UNLABELLED: Hearing loss is a very significant health problem. The methods currently available for inner ear drug delivery are limited and a noninvasive cell-specific drug delivery strategy needs to be found. AIM: In this study we investigated the ability of polymersomes, lipid core nanocapsules and hyperbranched poly-L-lysine to cross the round window membrane. MATERIALS & METHODS: Nanoparticles (NPs) used in this study have different size and chemical compositions. Freshly frozen human temporal bones were used for this investigation. Intact human round window membrane within the freshly frozen human temporal bone served as an excellent model to test the membrane permeation and distribution within the tissues. RESULTS: In this investigation we were able to visualize the NPs across the round window membrane. The NPs were subsequently found to be distributed in the sensory hair cells, nerve fibers and to other cells of the cochlea. CONCLUSION: This finding raises hope in terms of future multifunctional NP-based drug delivery strategy to the human inner ear.
Subject(s)
Drug Carriers/metabolism , Drug Delivery Systems/methods , Ear, Inner/metabolism , Nanocapsules/administration & dosage , Nanoparticles/analysis , Round Window, Ear/metabolism , Temporal Bone/metabolism , Cochlea/cytology , Cochlea/metabolism , Ear, Inner/cytology , Hair Cells, Auditory , Humans , Lipids , Nerve Fibers , Particle Size , Permeability , Polyesters/metabolism , Polylysine/metabolism , Tissue DistributionABSTRACT
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 ear.
