engleski

Cellular model of Parkinson’s disease for safety testing of gold-based nanodelivery system

Parkinson`s disease is the second most common neurodegenerative disorder (1). It is characterized by early prominent death of dopaminergic neurons in substantia nigra which results in classical motor symptoms of the disease: rigidity, rest tremor, bradykinesia, and postural instability (2). Although initially described more than 200 years ago (3), not a single drug is able to alter the natural history of the disease. Mainstay therapy is levodopa - a precursor in the synthesis of the dopamine - that can cross the blood brain barrier. Since introduction to the therapy, 50 years ago, many improvements have been made to enhance its efficiency and reduce side effects. However, passage of the blood brain barrier is still relatively poor, side effects can pose significant burden and long- term therapy is associated with motor complications. Motor complications are, at least in part, due to the fluctuations of levodopa concentrations in the plasma. In many cases these complications can be so intense that the only options is to discontinue the drug which inevitably leads to rapid decline in the quality of the life. Therefore, new formulations of levodopa, that can increase delivery of the drug to the brain and reduce plasma fluctuations are needed. This study tested the safety of phosphoglucomutase (PGM) functionalized gold nanoparticles (AuNP) as levodopa carrier using differentiated neuroblastoma (SH-SY5Y) cells as in vitro model of Parkinson`s disease. AuNPs shape, size, and surface charge were determined with transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements, respectively. Cell viability and apoptosis induction test were performed using flow cytometry, while oxidative stress was determined by measuring the concentration of reactive oxygen species, glutathione (GSH) and mitochondrial membrane potential. In all experiments levodopa loaded AuNPs were compared with AuNPs and levodopa alone.

Parkinson`s disease, gold nanoparticles

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