A Levodopa-Encapsulated Poly-ε-Caprolactone Nanocomposite Improves the Motor Symptoms and Neurochemical Changes in a Rotenone-Induced Mouse Model of Parkinson’s Disease

Parkinson's disease (PD) is the most common neurodegenerative disorder; in this condition, patients lose dopamine (DA), which leads to abnormal motor functions. Levodopa (LD) is the most effective drug used for the treatment of PD; however, LD shows poor plasma bioavailability and limited brain uptake and induces peripheral side effects. Due to its poor brain availability and short half-life, prolonged treatment must be repeated with a dosing schedule, which leads to long-term side effects, including dyskinesia, stomatitis, anxiety, and depression. An LD-encapsulated polymer nanocomposite has been reported to overcome these problems. The present study aims to improve the bioavailability and efficiency of LD to an effective treatment strategy for PD. Herein, we report the newly synthesized LD-encapsulated poly-ε-caprolactone (PCL) nanocomposite (LD-PCL-PVA NC), and its chemical and physical properties were analyzed. The LD-PCL-PVA NC exhibits no toxicity on the SH-SY5Y cell line and shows improved bioavailability of the LD in mouse plasma. Furthermore, we found that LD-PCL-PVA NC showed a significant improvement in motor symptoms in the rotenone (RT)-induced PD mouse model compared to the LD treatment. In addition, LD-PCL-PVA NC significantly increased the DA and homovanillic acid compared to LD and restored the total glutathione level and malonaldehyde and catalase activity in mouse brain. The histopathology studies reveal that LD-PCL-PVA NC did not exhibit toxicity in treated mice. The study suggested that LD-PCL-PVA NC can be used for the effective and promising treatment of PD.