From:  Updates on intranasal nanomedicine design for central nervous system disease treatment

 The key differences among various intranasal nanomedicines.

Optimization categorySpecific strategyKey differences
Surface engineeringMucoadhesive modification• Prolongs residence time.
• Extends the absorption window along olfactory/trigeminal pathways.
• Minimizes systemic exposure.
Permeation enhancement• Enhances mucosal penetration (especially for hydrophilic drugs).
• Significantly increases brain AUC and absorption rate (e.g., 2.25× increase).
Active targeting• Increases brain accumulation and bioavailability.
• Improves specific uptake of therapeutic agents (e.g., NAP peptide) in disease models.
Physicochemical propertiesSurface tension• Enhances wettability and mucus penetration ability.
Viscosity• Improves deposition rate within the olfactory region (ORF%).
Osmotic pressure• Prevents nasal irritation, dehydration, and mucosal injury.
• Avoids impaired drug absorption caused by hypertonicity (> 400 mOsm/kg).
Delivery deviceMedspray mist nozzle and other nozzles• Ensures uniform coverage of the nasal cavity.
• Higher deposition in the olfactory region (avoids vestibule accumulation).
• Narrower plume angles demonstrate superior drug delivery efficiency.
Droplet size control• Prevents inhalation into the lower respiratory tract (lung deposition).
• Ensures anterior nasal deposition.
In vivo fate factorsParticle size• Smaller particles facilitate transport via the trigeminal nerve pathway.
Surface charge• Enhances cellular uptake efficiency.
• Improves targeting efficiency via mucosal interaction.
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AUC: area under the curve.