Laboratory of Dynamics of Cellular Compartments, Instituto de Pesquisa e Desenvolvimento , Universidade do Vale do Paraiba , Sao Jose dos Campos 12244-000 , São Paulo , Brazil.
Department of Biochemistry, Neurobiology Laboratory, Escola Paulista de Medicina , Universidade Federal São Paulo , São Paulo 04021-00 , Brazil.
ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36693-36702. doi: 10.1021/acsami.8b12649. Epub 2018 Oct 22.
Delivering drugs and agents to the brain is a huge challenge, especially for chronic neurodegenerative disorders, such as Alzheimer's disease (AD). For this, prolonged and sustained release methods to increase brain uptake represent an impacting concept. The bioresorbable polymer poly-lactic acid (PLA) has high potential for medical implants; at the same time, glucagon-like peptide-1 (GLP-1) analogues have considerable neuroprotective attributes and represent a therapeutic strategy for AD. Here, a biodevice is produced by electrospinning PLA with a GLP-1 analogue (liraglutide, LG), coated with a thin layer of gelatin. The biodevice is subcutaneously implanted in a transgenic mouse model of AD and LG is released for 14 days in mice serum. After 4 weeks of implantation, crucial hallmarks of the AD are highly diminished: hippocampal senile amyloid β plaque load and neuroinflammatory markers. Furthermore, neurogenesis is enhanced in the subventricular zone, an important neurogenic niche in the brain. The designed biodevice holds great promise for being an affordable candidate to act as a prolonged drug provider, promoting LG mission through increasing its lifetime, constituting a relevant approach for old and impaired brain.
将药物和制剂递送到大脑是一个巨大的挑战，特别是对于慢性神经退行性疾病，如阿尔茨海默病（AD）。为此，延长和持续释放以增加大脑摄取的方法代表了一个有影响力的概念。可生物降解的聚合物聚乳酸（PLA）在医学植入物方面具有巨大的潜力；与此同时，胰高血糖素样肽-1（GLP-1）类似物具有相当大的神经保护特性，是 AD 的一种治疗策略。在这里，通过静电纺丝将 PLA 与 GLP-1 类似物（利拉鲁肽，LG）制成生物装置，并涂有一层薄薄的明胶。该生物装置被皮下植入 AD 的转基因小鼠模型中，LG 在小鼠血清中释放 14 天。植入 4 周后，AD 的关键特征大大减少：海马衰老淀粉样β斑块负荷和神经炎症标志物。此外，侧脑室下区的神经发生增强，这是大脑中一个重要的神经发生龛。设计的生物装置具有成为一种负担得起的、可延长药物输送的候选物的巨大潜力，通过延长其寿命来促进 LG 的使命，为老化和受损的大脑提供了一种相关的方法。
