Although new OSN regrow in the gaps, the clefts may still allow an efficient drug uptake for larger particles. dependent on the presence of the IgGs antigen. In summary, it was successfully exhibited that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential. nerve bundles enclosed by olfactory ensheathing cells (OEC) and olfactory nerve fibroblasts. OECs are suggested to be a part of the innate immune system and their uptake of particles is well described [18,19]. The ensheathed nerve bundles travel through the cribriform plate of the ethmoid bone into the CNS where they terminate at the olfactory bulb. Hence, OSN are outstanding neurons that have their cell bodies located in a distal epithelium while their non-motile cilia processes extend into the mucus and allow them to be in direct ICG-001 contact with the environment. Interestingly, the olfactory nerve bundles appear to play a major role in N2B drug delivery. The intranasal delivery of drugs to the CNS has been pinpointed to the upper third of the nasal cavity, thus the olfactory region [4,6,12]. To reach the nerves, the drug must pass the epithelial tight junctions, which poses a hurdle that could limit the drug uptake . However, the neuronal turnover within the olfactory epithelial layer is rather high, and dying cells may leave a gap that renders the epithelium sufficiently porous . ICG-001 Although new OSN regrow in the gaps, the clefts may still allow an efficient drug uptake for larger particles. In addition, the formation of tight junctions lining the apical layer has been reported to be delayed . Despite these observations, it should be noted that this passage through the does not consequently imply that the total applied dose of the drug will arrive in the CNS. It may also be assimilated by blood vessels, enter glands, lymphatic/glymphatic FANCC vessels, the cranial nerves or interact with mucosal immune cells . However, mathematical predictions strongly suggest a transport along the olfactory and trigeminal neural pathways . Taking the trigeminal or olfactory route, the drug can reach the subarachnoid space adjacent to the pons or the olfactory bulb. From here, the further distribution of a drug in the CNS appears to be mediated via bulk flow of the CSF . Owing to the promising features of intranasally delivered CNS-active drugs, there has been a rise in publications on intranasal drug delivery experiments in rodents. However, a literature search on in vivo experiments that use intranasal ICG-001 drug delivery has revealed one concerning condition. Nearly every intranasal administration approach is performed by pouring a drop of drug ICG-001 answer onto, or into, the nostril of a mouse or rat. In this scenario, even the administration of volumes of 20 L, or less, lead to a flooding of the murine nostril, so that ICG-001 the total amount of deposited drug remains unknown. Furthermore, this approach is also accompanied with safety issues for the laboratory animals such as the swallowing or inhalation of administered drug answer. Further, the assessment of pharmacokinetic data and of quantitative readouts cannot be determined when using this conventional technique . Recently, the authors of this study have suggested a region-specific administration approach utilizing a catheter to either target the respiratory or olfactory mucosa . This approach was developed with the aid of a 3D cast of the murine nasal cavity. As the flow chart in Physique 1 summarizes, the conventional and refined region-specific intranasal administration were first compared to examine the novel administration approach in more detail and to verify its suitability and feasibility. Then, the potential uptake to the periphery after intranasal delivery was explored. Here, insulin was used as it is usually well described with.
Although new OSN regrow in the gaps, the clefts may still allow an efficient drug uptake for larger particles