Abstract
Nose-to-central nervous system (CNS) drug delivery has shown promising results in preclinical efficacy models and exploratory human clinical trials. There are two primary limitations to direct CNS uptake of drugs following intranasal administration. Firstly, non-specific deposition in the nasal cavity leads to systemic absorption instead of CNS absorption, altering CNS bioavailability. Secondly, mucociliary clearance affects the residence time of the formulation at the site of deposition. In vivo results have demonstrated that therapeutic agents targeted to the olfactory region can translocate directly into the CNS via neuronal uptake. In this review, liquid and solid formulations are investigated for their effect on olfactory deposition and clearance based on their physical properties. The influence of delivery device and mode of administration is also reviewed. Case examples are provided to illustrate the importance of optimal deposition in olfactory region.
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