Strategies for drug delivery to the human inner ear by multifunctional nanoparticles
University of Innsbruck, Innsbruck, Tyrol, AustriaNanomedicine (Impact Factor: 5.41). 11/2011; 7(1):55-63. DOI: 10.2217/nnm.11.84
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.
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ABSTRACT: Neurology deals with the study and management of disorders of the nervous system. Considerable research is in progress in basic neurosciences and clinical neurology. The management is mostly medical. Many neurological disorders require surgical intervention, and the closely related specialty of surgical neurology or neurosurgery will also be considered in this chapter. There is a considerable scope for application of nanobiotechnology in neurology and hence the term nanoneurology (Jain 2009a). Nanobiotechnology has been applied for neurophysiological studies, diagnosis, neuropharmacology, and refinement of surgical tools. Neuroprotection is an important objective in treatment of diseases of the central nervous system (CNS).
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ABSTRACT: Background: Due to their biochemical versatility, nanoparticles (NPs) have become one of the most important future carriers for drugs and genes. NP-mediated delivery could enable an effective pharmacotherapy to the inner ear and combat hearing loss. Aims: This study investigates the endocytic trafficking of silica NPs within HEI-OC1 cells, a cell line derived from the inner ear. Materials & methods: To investigate the interaction between 50-, 70- and 100-nm silica NPs and the cells, the authors employed a set of commonly available methods involving light and electron microscopy, and sample processing methods, which preserve the native cell shape and the fragile endocytic structures. Results: The authors observed that 50-nm NPs were the most efficiently internalized. They also identified macropinocytosis as the dominant mechanism of uptake, showed localization of NPs in the early endosome and observed that silica NPs were delayed during trafficking to the lysosomes, where these NPs stayed confined, showing no endosomal escape. Conclusion: These silica NPs mostly rely on macropinocytosis for internalization. A successful use of silica NPs as vectors would involve smaller NPs and an endosomal escape strategy. Original submitted 21 December 2011; Revised submitted 23 May 2012.
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ABSTRACT: For many years, drug delivery to the inner ear has been a challenge to physicians in the treatment of inner ear disorders. In the past decade, the field of inner ear drug delivery has emerged with the development of new biomaterials and drug delivery technologies to improve the effectiveness of inner ear drug therapy. This paper reviews a number of inner ear drug delivery strategies including systemic, intratympanic, and intracochlear delivery. A focus of this review is the recent advances in intratympanic delivery of medications; approaches utilizing novel biomaterials as well as other recent developments are also discussed. Biotechnology-based approaches, such as gene and stem cell therapy methods are also reviewed. Among the various strategies, local drug delivery approaches including intratympanic and intracochlear drug delivery methods that limit systemic exposure are particularly promising. These inner ear drug delivery systems provide a new opportunity to improve the treatment of inner ear disorders.
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