Nose-to-Brain Transport Pathways of Wheat Germ Agglutinin Conjugated PEG-PLA Nanoparticles

Purpose To investigate the possible pathways for transport of wheat germ agglutinin conjugated PEG-PLA nanoparticles (WGA-NP) into the brain after nasal administration. Methods The nose-to-brain pathways were investigated using WGA-NP containing 6-coumarin (as a fluorescent marker) and 125 I-labeled WGA-NP. Ex vivo imaging analysis was also employed to visualize the transport process. Results Nasal administration of WGA-NP to rats resulted in transcellular absorption across the olfactory epithelium and transfer to the olfactory bulb within 5 min. After entering the lamina propria, a proportion of WGA-NP were transferred from the olfactory nerve bundles and their surrounding connective tissue to the olfactory bulb. The trigeminal nerves also contributed to WGA-NP brain transfer, especially to WGA-NP distribution in the caudal brain areas. However, cerebrospinal fluid pathway may have little contribution to the process of transferring WGA-NP into the central nervous system (CNS) after intranasal administration. Conclusions These results demonstrated that intranasally administered WGA-NP reach the CNS via olfactory pathway and trigeminal nerve pathway, and extracellular transport along these nerves is the most possible mechanism.