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

• Published in: Nano research 2021-08, Vol.14 (8), p.2749-2761
• Main Authors: Nie, Tianqi, He, Zhiyu, Zhu, Jinchang, Chen, Kuntao, Howard, Gregory P., Pacheco-Torres, Jesus, Minn, Il, Zhao, Pengfei, Bhujwalla, Zaver M., Mao, Hai-Quan, Liu, Lixin, Chen, Yongming
• Format: Article
• Language: English
• Subjects: Atomic/Molecular Structure and Spectra; Biocompatibility; Biomedicine; Biotechnology; Brain; Cardiovascular diseases; Chemistry and Materials Science; Condensed Matter Physics; Dihydroxyphenylalanine; Dopamine; Dopamine receptors; Health risks; Health services; Homocysteine; Hydrogen bonding; Hydroxylase; Inflammation; Levodopa; Materials Science; Movement disorders; Nanoparticles; Nanotechnology; Neurodegenerative diseases; Oral administration; Organs; Oxidative stress; Parkinson's disease; Peripheral circulation; Pharmacodynamics; Polyvinyl alcohol; Research Article; Tannic acid; Tyrosine; Tyrosine 3-monooxygenase
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-020-3280-0

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.