Highly stabilized nanocrystals delivering Ginkgolide B in protecting against the Parkinson’s disease

• Published in: International journal of pharmaceutics 2020-03, Vol.577, p.119053-119053, Article 119053
• Main Authors: Liu, Yao, Liu, Wei, Xiong, Sha, Luo, Jingshan, Li, Ye, Zhao, Yuying, Wang, Qun, Zhang, Zexin, Chen, Xiaojia, Chen, Tongkai
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Drug delivery; Gastrointestinal tract; Nanocrystals; Parkinson’s disease
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119053

[Display omitted] 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.