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

Research output: Contribution to journalArticlepeer-review

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. [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalNano Research
DOIs
StateAccepted/In press - 2021

Keywords

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

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

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