Intranasal Application of Peptides Modulating the Neuropeptide Y System

Area of Science:

• Neuroscience
• Pharmacology
• Drug Delivery

Background:

• Neuropeptide Y (NPY) system is crucial for physiological functions.
• NPY Y1 and Y2 receptors are targets for weight and mental disorder treatments.
• Nose-to-brain delivery offers a route to bypass challenges in peptide delivery to the brain.

Purpose of the Study:

• To evaluate fluorescently labeled NPY peptides for selective Y1R and Y2R activation.
• To assess the stability and nasal permeability of these peptides.
• To investigate the in vivo uptake and distribution of selected peptides after intranasal administration.

Main Methods:

• Utilized Calu-3 cells as a nasal mucosa model to test peptide permeability.
• Combined permeability and receptor activation assays to confirm intact peptide translocation.
• Employed whole slide scanning and confocal microscopy for in vivo imaging of intranasally administered peptides.

Main Results:

• Demonstrated stability and successful translocation of intact fluorescently labeled peptides across the Calu-3 cell model.
• Confirmed selective targeting of Y1R or Y2R by the developed compounds.
• Quantified rapid peptide uptake (within 15 min) and sustained presence (up to 24 h) in vivo.

Conclusions:

• Cell-based and in vivo studies successfully identified peptides with high pharmacological potential for nasal delivery.
• The study validates nose-to-brain delivery of NPY receptor-targeting peptides for therapeutic applications.
• Confocal microscopy provides superior signal-to-noise ratio for in vivo peptide detection compared to whole slide scanning.