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.
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.
Authors: M Boulton; A Young; J Hay; D Armstrong; M Flessner; M Schwartz; M Johnston Journal: Neuropathol Appl Neurobiol Date: 1996-08 Impact factor: 8.090
Authors: Ann F Hubbs; Linda M Sargent; Dale W Porter; Tina M Sager; Bean T Chen; David G Frazer; Vincent Castranova; Krishnan Sriram; Timothy R Nurkiewicz; Steven H Reynolds; Lori A Battelli; Diane Schwegler-Berry; Walter McKinney; Kara L Fluharty; Robert R Mercer Journal: Toxicol Pathol Date: 2013-02-06 Impact factor: 1.902