title: Nose-to-brain transport pathways of wheat germ agglutinin conjugated PEG-PLA nanoparticles.
abstract: OBJECTIVE
  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.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Room 604, Shanghai, 201203, People's Republic of China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.forename: Yehong
authors.initials: Y
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Feng
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D003374:Coumarins / Q000008:administration & dosage / Q000032:analysis; D053758:Nanoparticles / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000032:analysis; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry
chemical_list: D003374:Coumarins; D013844:Thiazoles; D014909:Wheat Germ Agglutinins; C517282:coumarin 6; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols