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Nanotechnology seems to play a very important role in the diagnosis and treatment of various diseases and disorders. Although various nanomedicines have been developed and are in the marketplace to overcome the challenges associated with their conventional counterparts, still different obstacles such as toxicity, scale-up, and regulatory concerns have not been resolved fully to understand better the development of nanomedicines. Here, in the current chapter, we tried to mention translational challenges of toxicity, mechanism, assessment, and different strategies to overcome different toxicities. We believe that knowing the challenges early in the drug development will always encourage the investment in commercial production of nanotechnology-based formulations. Overall, this chapter elucidates the various toxicity aspects of nanomedicine to know the impact of toxicity aiming to foster clinical translation of nanomedicines especially in “nose-to-brain” delivery.

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