Mallamaci Rosanna, Musarò Debora, Greco Marco, Caponio Antonello, Castellani Stefano, Munir Anas, Guerra Lorenzo, Damato Marina, Fracchiolla Giuseppe, Coppola Chiara, Cardone Rosa Angela, Rashidi Mehdi, Tardugno Roberta, Sergio Sara, Trapani Adriana, Maffia Michele
Department of Biosciences, Biotechnologies and Environment, University of Bari "Aldo Moro", 70125 Bari, Italy.
Department of Biological and Environmental Science and Technology, University of Salento, Via Lecce-Monteroni, 73100 Lecce, Italy.
Molecules. 2024 Apr 13;29(8):1774. doi: 10.3390/molecules29081774.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.
帕金森病（PD）是一种常见的神经退行性疾病，主要与黑质中多巴胺能神经元的耗竭有关。目前的治疗重点是补偿多巴胺（DA）缺乏，但血脑屏障（BBB）对有效药物递送构成挑战。我们使用分化的SH-SY5Y细胞，研究了DA与抗氧化剂葡萄籽提取物（GSE）的联合给药，以研究细胞生物相容性、对神经毒素鱼藤酮的细胞保护作用及其抗氧化作用。为此，合成了两种固体脂质纳米粒（SLN）制剂，即DA-co-GSE-SLNs和GSE-ads-DA-SLNs。根据所检测的制剂，此类SLN的平均粒径在187-297nm范围内，ζ电位值在-4.1--9.7mV范围内，DA结合效率在35%至82%之间。结果表明，DA/GSE-SLNs不会改变细胞活力，对鱼藤酮诱导的毒性和氧化应激具有细胞保护作用。此外，本研究还重点评估了α-突触核蛋白（aS）水平；SLNs显示出调节鱼藤酮介导的aS水平升高的潜力。总之，我们的研究调查了SLNs作为治疗PD的递送系统的潜力，这也代表了一种增强药物和抗氧化分子跨血脑屏障递送的有前景的方法。
