Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease
| Autor: | Tianqi Nie, Lixin Liu, Zhiyu He, Jinchang Zhu, Il Minn, Jesus Pacheco-Torres, Kuntao Chen, Pengfei Zhao, Gregory P. Howard, Hai-Quan Mao, Yongming Chen, Zaver M. Bhujwalla |
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| Rok vydání: | 2021 |
| Předmět: |
Levodopa
Parkinson's disease Inflammation 02 engineering and technology Pharmacology 010402 general chemistry medicine.disease_cause 01 natural sciences Oral administration Dopamine Medicine General Materials Science Electrical and Electronic Engineering Tyrosine hydroxylase business.industry 021001 nanoscience & nanotechnology Condensed Matter Physics medicine.disease Atomic and Molecular Physics and Optics 0104 chemical sciences Pharmacodynamics medicine.symptom 0210 nano-technology business Oxidative stress medicine.drug |
| Zdroj: | Nano Research. 14:2749-2761 |
| ISSN: | 1998-0000 1998-0124 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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