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 language | English (US) |
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Pages (from-to) | 2749-2761 |
Number of pages | 13 |
Journal | Nano Research |
Volume | 14 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2021 |
Keywords
- Parkinson’s disease
- brain delivery
- cerebral lymphatic vasculature
- levodopa
ASJC Scopus subject areas
- Atomic and Molecular Physics, and Optics
- Materials Science(all)
- Condensed Matter Physics
- Electrical and Electronic Engineering