Effect of particle size and surface charge on nanoparticles diffusion in the brain white matter

Tian Yuan*, Ling Gao, Wenbo Zhan, Daniele Dini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
3 Downloads (Pure)


Brain disorders have become a serious problem for healthcare worldwide. Nanoparticle-based drugs are one of the emerging therapies and have shown great promise to treat brain diseases. Modifications on particle size and surface charge are two efficient ways to increase the transport efficiency of nanoparticles through brain-blood barrier; however, partly due to the high complexity of brain microstructure and limited visibility of Nanoparticles (NPs), our understanding of how these two modifications can affect the transport of NPs in the brain is insufficient.

In this study, a framework, which contains a stochastic geometric model of brain white matter (WM) and a mathematical particle tracing model, was developed to investigate the relationship between particle size/surface charge of the NPs and their effective diffusion coefficients (D) in WM.

The predictive capabilities of this method have been validated using published experimental tests. For negatively charged NPs, both particle size and surface charge are positively correlated with D before reaching a size threshold. When Zeta potential (Zp) is less negative than -10 mV, the difference between NPs’ D in WM and pure interstitial fluid (IF) is limited.

A deeper understanding on the relationships between particle size/surface charge of NPs and their D in WM has been obtained. The results from this study and the developed modelling framework provide important tools for the development of nano-drugs and nano-carriers to cure brain diseases.
Original languageEnglish
Pages (from-to)767–781
Number of pages15
JournalPharmaceutical Research
Early online date21 Mar 2022
Publication statusPublished - Apr 2022

Bibliographical note

This project has received funding from the European Unions Horizon 2020 research and innovation programme under Grant Agreement No. 688279. Daniele Dini would like to acknowledge the support received from the EPSRC under the Established Career Fellowship Grant No. EP/N025954/1. Tian Yuan would also like to acknowledge financial support from CSC Imperial Scholarship. The authors declare that they have no conflict of interest.


  • Brain diseases
  • Brain tissue
  • Diffusion coefficient
  • Extracellular space
  • Nanoparticles


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