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Nose-to-brain delivery has gained significant interest over the past several decades. This has resulted in numerous strategies described to improve the delivery of drugs to the brain directly through the olfactory epithelium of the nasal cavity. In some cases, intranasal administration may be more effective than other routes of administration in treating central nervous system and related disorders. Here, we briefly review the strategies that have been used to facilitate nose-to-brain delivery as well as approaches to block the delivery of drugs from the nose to the brain. Even though numerous strategies have already been used to increase nose-to-brain delivery, the research for strategies inhibitory of nose-to-brain delivery seems to be scarce., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Franz cell (FC) experiments in topical and transdermal drug development represent the gold standard in vitro method but require a relatively high quantity of human skin, are low-throughput, and are time-consuming to perform. To address these issues, we studied a micro-well plate-based screening method for permeability and retention that could enable the direct screening of large numbers of formulations simultaneously across human skin. Using freshly excised dermatomed human skin modified to reflect poor barrier function and a model hydrophilic compound, Sulforhodamine B (SRB), FC permeation and retention quantification was compared to the 96-well high-throughput system (HTS). The skin was analyzed using 2-photon microscopy to determine the drug distribution within the skin. A screen of 15 different formulations in triplicate in a single piece of human skin, using full factorial design was then conducted. Permeability of SRB across the skin as well as the drug distribution profile of SRB retained in the skin were similar for the FC and HTS system. The influence of different excipients on drug retention was observed in the full factorial formulation screen. The HTS method is promising for the investigation of large numbers of formulations and the influence of formulations changes in skin retention of drug., (Copyright © 2019 Elsevier B.V. All rights reserved.)