Role of Tissue Hydraulic Permeability in Convection-Enhanced Delivery of Nanoparticle-Encapsulated Chemotherapy Drugs to Brain Tumour

Yi Yang, Wenbo Zhan* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Purpose
Tissue hydraulic permeability of brain tumours can vary considerably depending on the tissue microstructure, compositions in interstitium and tumour cells. Its effects on drug transport and accumulation remain poorly understood.

Methods
Mathematical modelling is applied to predict the drug delivery outcomes in tumours with different tissue permeability upon convection-enhanced delivery. The modelling is based on a 3-D realistic tumour model that is extracted from patient magnetic resonance images.

Results
Modelling results show that infusing drugs into a permeable tumour can facilitate a more favourable hydraulic environment for drug transport. The infused drugs will exhibit a relatively uniform distribution and cover a larger tumour volume for effective cell killing. Cross-comparisons show the delivery outcomes are more sensitive to the changes in tissue hydraulic permeability and blood pressure than the fluid flow from the brain ventricle. Quantitative analyses demonstrate that increasing the fluid gain from both the blood and brain ventricle can further improve the interstitial fluid flow, and thereby enhance the delivery outcomes. Furthermore, similar responses to the changes in tissue hydraulic permeability can be found for different types of drugs.

Conclusions
Tissue hydraulic permeability as an intrinsic property can influence drug accumulation and distribution. Results from this study can deepen the understanding of the interplays between drug and tissues that are involved in the drug delivery processes in chemotherapy.
Original languageEnglish
Pages (from-to)877-892
JournalPharmaceutical Research
Volume39
Issue number5
Early online date26 Apr 2022
DOIs
Publication statusPublished - 1 Jun 2022

Keywords

  • brain tumour
  • convection-enhanced delivery
  • drug transport
  • mathematical modelling
  • tissue hydraulic permeability

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