Abstract：
Parkinson\'s disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in Cmax, Tmax, and AUC0 - t values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug\'s efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy.
摘要：
帕金森病（PD），影响全球数百万人，预计到2030年将影响1000万人，这表明一系列与多巴胺能神经元下降有关的运动和非运动症状。目前的治疗方法可以控制PD症状，但在减缓疾病进展方面缺乏疗效。强调更有效治疗的紧迫性。白藜芦醇（RSV），公认的神经保护和抗氧化特性，由于生物利用度有限，PD的临床应用面临挑战。研究人员研究了基于脂质的纳米制剂，特别是固体脂质纳米颗粒（SLN），增强RSV稳定性。通过SLN的口服药物递送面临障碍，提示探索使用与微针（MNs）集成的SLN经皮给药，以改善患者的依从性。在这项研究中,结合到MN贴剂中的RSV-SLN(RSV-SLN)被开发用于经皮RSV递送,以提高其稳定性和患者依从性。表征研究表明SLN具有78.36±0.74%的持续药物释放曲线的有利物理性质。开发的MN表现出机械坚固性和皮肤穿透能力。离体渗透研究显示68.39±1.4%的药物通过皮肤的大量渗透。在体内药代动力学研究中，通过MN递送的RSV-SLN表现出Cmax的显著增加，Tmax,和AUC0-t值，与通过MNs施用纯RSV相比，血浆清除率降低。此外，一项体内研究表明，在接受治疗的动物中，行为功能增强，大脑抗氧化剂水平增加。体内皮肤刺激研究显示直到24小时都没有刺激迹象，这允许长期应用MNs。组织病理学分析显示大鼠脑区有显著变化，特别是纹状体和黑质，治疗完成后。基于这些发现,RSV-SLN加载的MN(RSVSNLMP)补丁的开发提出了一种新颖的方法，具有提高药物效率的潜力，患者依从性,和PD的治疗结果，为高级PD治疗提供了一个有希望的途径。
