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Nano Research

Article Title

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

Authors

Tianqi Nie, 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
Zhiyu He, Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100, ChinaFollow
Jinchang Zhu, Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Kuntao Chen, Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Gregory P. Howard, Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA
Jesus Pacheco-Torres, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Il Minn, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Pengfei Zhao, 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
Zaver M. Bhujwalla, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Hai-Quan Mao, Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD 21287, USAFollow
Lixin Liu, 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
Yongming Chen, School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, ChinaFollow

Keywords

levodopa, brain delivery, cerebral lymphatic vasculature, Parkinson’s disease

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.

Publisher

Tsinghua University Press

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