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

  • Int J Pharm. 2020 Mar 15;577:119053. doi: 10.1016/j.ijpharm.2020.119053.
Yao Liu  1 ,  Wei Liu  1 ,  Sha Xiong  1 ,  Jingshan Luo  1 ,  Ye Li  2 ,  Yuying Zhao  1 ,  Qun Wang  1 ,  Zexin Zhang  3 ,  Xiaojia Chen  4 ,  Tongkai Chen  5
Affiliations
  • 1. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 2. Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  • 3. The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 4. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: [email protected].
  • 5. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: [email protected].
PMID: 31981707 DOI: 10.1016/j.ijpharm.2020.119053
Abstract

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.

Keywords
Blood-brain barrier; Drug delivery; Gastrointestinal tract; Nanocrystals; Parkinson’s disease.
Products