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

Tianqi Nie; Zhiyu He; Jinchang Zhu; Kuntao Chen; Gregory P. Howard; Jesus Pacheco-Torres; Il Minn; Pengfei Zhao; Zaver M. Bhujwalla; Hai-Quan Mao; Lixin Liu; Yongming Chen

doi:10.1007/s12274-020-3280-0

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Research Article

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

Tianqi Nie^{¹^,^§}, Zhiyu He^{²^,^§}(

), Jinchang Zhu^³, Kuntao Chen^³, Gregory P. Howard^{⁴^,⁵}, Jesus Pacheco-Torres^⁶, Il Minn^{⁵^,⁶}, Pengfei Zhao^¹, Zaver M. Bhujwalla^⁶, Hai-Quan Mao^{³^,⁴^,⁵^,⁷}(

), Lixin Liu^¹, Yongming Chen^¹(

)

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

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

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

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

5Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA

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

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

^§ Tianqi Nie and Zhiyu He contributed equally to this work.

Show Author Information

Graphical Abstract

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.

Keywords

levodopa brain delivery cerebral lymphatic vasculature Parkinson’s disease

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Nano Research

Volume 14 Issue 8,
August 2021

Pages 2749-2761

DOI: 10.1007/s12274-020-3280-0

Cite this article:

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 Research, 2021, 14(8): 2749-2761. https://doi.org/10.1007/s12274-020-3280-0

Topics:

Biocompatibility Controlled drug delivery Hydrogen bonds Nanoparticles Neurons Targeted drug delivery

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Received: 22 September 2020

Revised: 27 November 2020

Accepted: 02 December 2020

Published: 05 January 2021