Nose-to-brain transport pathways of wheat germ agglutinin conjugated PEG-PLA nanoparticles.

Qingfeng Liu, Yehong Shen, Jie Chen, Xiaoling Gao, Chengcheng Feng, Lu Wang, Qizhi Zhang, Xinguo Jiang

Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Room 604, Shanghai, 201203, People's Republic of China.

Pharmaceutical research 2012 Feb

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To investigate the possible pathways for transport of wheat germ agglutinin conjugated PEG-PLA nanoparticles (WGA-NP) into the brain after nasal administration. 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. 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. 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.

Citation

Qingfeng Liu, Yehong Shen, Jie Chen, Xiaoling Gao, Chengcheng Feng, Lu Wang, Qizhi Zhang, Xinguo Jiang. Nose-to-brain transport pathways of wheat germ agglutinin conjugated PEG-PLA nanoparticles. Pharmaceutical research. 2012 Feb;29(2):546-58