Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
Int J Pharm. 2020 Mar 15;577:119053. doi: 10.1016/j.ijpharm.2020.119053. Epub 2020 Jan 22.
As a major cause of neurodegeneration in the elderly, Parkinson's disease (PD) has attracted intense research attention. PD results from a decline in the numbers of dopaminergic neurons. Due to low levels of plasma exposure and the drug efflux properties of neuronal cells, orally delivering anti-PD drugs is challenging. Nanocrystals (NCs) can increase dissolution velocities and saturation solubility, improving oral bioavailability and brain uptake. In this study, Ginkgolide B (GB), a potent anti-Parkinsonism compound, was selected to verify the utility of NCs to effectively accumulate GB in both the blood and brain. Highly stabilized GB-NCs had small sizes, high rates of dissolution, enhanced cellular uptake and permeability. The GB-NCs could protect neurons against cytotoxicity induced by MPP, and showed no toxicity in zebrafish. Fluorescent imaging in zebrafish indicated high levels of the NCs in both the gut and brain. When orally administrated to rats, the GB-NCs showed higher drug plasma levels and neuronal drug distributions when compared to control groups. Importantly, in MPTP-induced PD model, GB-NCs treatment resulted in improved behavior, reduced dopamine deficiency, and elevated dopamine metabolite levels. In summary, these highlight the fabrication of GB-NCs as effective drug carriers for the neuronal delivery of anti-PD therapies.
作为老年人神经退行性疾病的主要病因，帕金森病（PD）引起了人们的强烈关注。PD 是由于多巴胺能神经元数量减少引起的。由于血浆暴露水平低和神经元细胞的药物外排特性，口服给予抗 PD 药物具有挑战性。纳米晶体（NCs）可以提高溶解速度和饱和溶解度，从而提高口服生物利用度和脑内摄取。在这项研究中，选择银杏内酯 B（GB）作为一种有效的抗帕金森病化合物，以验证 NCs 有效积聚 GB 于血液和脑中的效用。高度稳定的 GB-NCs 具有较小的尺寸、较高的溶解速率、增强的细胞摄取和通透性。GB-NCs 可以保护神经元免受 MPP 诱导的细胞毒性，并且在斑马鱼中没有毒性。斑马鱼的荧光成像表明 NCs 在肠道和大脑中均有高水平积聚。当以口服方式给予大鼠时，与对照组相比，GB-NCs 组的药物血浆水平和神经元药物分布更高。重要的是，在 MPTP 诱导的 PD 模型中，GB-NCs 治疗可改善行为，减少多巴胺缺乏，并提高多巴胺代谢物水平。总之，这些研究突出了 GB-NCs 的制备作为神经元传递抗 PD 治疗的有效药物载体。
