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Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease

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Abstract

Levodopa (L-DOPA), a precursor of dopamine, is commonly prescribed for the treatment of the Parkinson’s disease (PD). However, oral administration of levodopa results in a high level of homocysteine in the peripheral circulation, thereby elevating the risk of cardiovascular disease, and limiting its clinical application. Here, we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature. The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid (TA)/polyvinyl alcohol (PVA) via hydrogen bonding using the flash nanocomplexation (FNC) process, resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner. Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase, which indicate the dopaminergic neuron functions, were increased by 2- and 4-fold, respectively. Movement disorders and cerebral oxidative stress of the rats were significantly improved. This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs. This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.

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Acknowledgements

This work was partially supported by Natural Science Foundation of China (No. 51533009), the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2013S086) and the key Area Research and Development of Guangzhou (No. 202007020006).

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Author notes

  1. Tianqi Nie and Zhiyu He contributed equally to this work.

Authors and Affiliations

  1. School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, 510275, China

    Tianqi Nie, Pengfei Zhao, Lixin Liu & Yongming Chen

  2. Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao, 266100, China

    Zhiyu He

  3. Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA

    Jinchang Zhu, Kuntao Chen & Hai-Quan Mao

  4. Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

    Gregory P. Howard & Hai-Quan Mao

  5. Institute for Nano Bio Technology, Johns Hopkins University, Baltimore, MD, 21218, USA

    Gregory P. Howard, Il Minn & Hai-Quan Mao

  6. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

    Jesus Pacheco-Torres, Il Minn & Zaver M. Bhujwalla

  7. Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA

    Hai-Quan Mao

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  1. Tianqi Nie
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Correspondence to Zhiyu He, Hai-Quan Mao or Yongming Chen.

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Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease

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Nie, T., He, Z., Zhu, J. et al. Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease. Nano Res. 14, 2749–2761 (2021). https://doi.org/10.1007/s12274-020-3280-0

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