Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, 70910-900, Brazil.
Departamento de Biologia Animal e Plantas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86051-970, Brazil.
Sci Rep. 2021 Jul 26;11(1):15185. doi: 10.1038/s41598-021-94175-8.
Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes. Our goal was to design and test the neurotherapeutic potential of a forefront nanoparticle-based technology composed of albumin/PLGA nanosystems loaded with dopamine (ALNP-DA) in 6-OHDA PD mice model. ALNP-DA effectively crossed the BBB, replenishing dopamine at the nigrostriatal pathway, resulting in significant motor symptom improvement when compared to Lesioned and L-DOPA groups. Notably, ALNP-DA (20 mg/animal dose) additionally up-regulated and restored motor coordination, balance, and sensorimotor performance to non-lesioned (Sham) animal level. Overall, ALNPs represent an innovative, non-invasive nano-therapeutical strategy for PD, considering its efficacy to circumvent the BBB and ultimately deliver the drug of interest to the brain.
帕金森病（PD）是一种中枢神经系统进行性和慢性神经退行性疾病。早期治疗 PD 是有效的；然而，长期系统性药物治疗通常会导致有害的副作用。使用较小剂量、穿过复杂的血脑屏障（BBB），将药物更有选择性地递送到大脑的策略是非常可取的，以确保治疗效果并减少/避免不良后果。我们的目标是设计和测试由载有多巴胺的白蛋白/PLGA 纳米系统组成的前沿纳米颗粒技术（ALNP-DA）在 6-OHDA PD 小鼠模型中的神经治疗潜力。ALNP-DA 有效地穿过 BBB，在黑质纹状体通路补充多巴胺，与损伤和 L-DOPA 组相比，运动症状显著改善。值得注意的是，ALNP-DA（20mg/动物剂量）还上调并恢复了运动协调、平衡和感觉运动性能，达到非损伤（Sham）动物水平。总的来说，ALNPs 代表了一种创新的、非侵入性的纳米治疗策略，用于治疗 PD，因为它能够绕过 BBB，并最终将治疗药物递送到大脑。
