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

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Abstract

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 125I-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.

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Acknowledgments & DISCLOSURES

This work was supported by National Natural Science Foundation of China (No.30772657), National Basic Research Program of China (No. 2007CB935802), and National Science and Technology Major Project (2009ZX09310-006).

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Authors and Affiliations

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

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

  2. Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Shanghai, People’s Republic of China, 201203

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

  3. Department of Pharmacology, College of Basic Medical Sciences, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China

    Xiaoling Gao

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  1. Qingfeng Liu
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Correspondence to Qizhi Zhang.

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Liu, Q., Shen, Y., Chen, J. et al. Nose-to-Brain Transport Pathways of Wheat Germ Agglutinin Conjugated PEG-PLA Nanoparticles. Pharm Res 29, 546–558 (2012). https://doi.org/10.1007/s11095-011-0641-0

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  • DOI: https://doi.org/10.1007/s11095-011-0641-0

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