Hanumanthappa Ramesha, Heggannavar Geetha B, Banakar Aishwarya, Achari Divya D, Ramesh Karoshi Vijaykumar, Krushna B R Radha, Bepari Asmatanzeem, Assad Assiri Rasha, Nasser Altamimi Hanan, Nanjaiah Hemalatha, Sannaningaiah Devaraja, Raghu Shamprasad Varija, Kaveeshwar Vishwas, Nagabhushana H, Devaraju Kuramkote Shivanna
Neuro-Chemistry Lab, Department of Biochemistry, Karnatak University, Dharwad, Karnataka 580003, India.
Department of Chemistry, Karnatak University, Dharwad, Karnataka 580003, India.
ACS Omega. 2025 May 6;10(19):19682-19696. doi: 10.1021/acsomega.5c00691. eCollection 2025 May 20.
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.
帕金森病（PD）是最常见的神经退行性疾病；在这种疾病中，患者会失去多巴胺（DA），这会导致运动功能异常。左旋多巴（LD）是治疗帕金森病最有效的药物；然而，左旋多巴的血浆生物利用度较差，脑摄取有限，并会引发外周副作用。由于其脑内可利用性差且半衰期短，必须按照给药方案重复进行长期治疗，这会导致包括运动障碍、口腔炎、焦虑和抑郁在内的长期副作用。据报道，一种包裹左旋多巴的聚合物纳米复合材料可克服这些问题。本研究旨在提高左旋多巴的生物利用度和疗效，以形成一种有效的帕金森病治疗策略。在此，我们报告了新合成的包裹左旋多巴的聚ε-己内酯（PCL）纳米复合材料（LD-PCL-PVA NC），并对其化学和物理性质进行了分析。LD-PCL-PVA NC对SH-SY5Y细胞系无毒性，且在小鼠血浆中显示出左旋多巴生物利用度的提高。此外，我们发现与左旋多巴治疗相比，LD-PCL-PVA NC在鱼藤酮（RT）诱导的帕金森病小鼠模型中，运动症状有显著改善。另外，与左旋多巴相比，LD-PCL-PVA NC显著增加了多巴胺和高香草酸，并恢复了小鼠脑内的总谷胱甘肽水平、丙二醛水平和过氧化氢酶活性。组织病理学研究表明，LD-PCL-PVA NC在治疗小鼠中未表现出毒性。该研究表明，LD-PCL-PVA NC可用于有效且有前景的帕金森病治疗。
