Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery

Wenbo Zhan (Corresponding Author), Ferdinando Rodriguez y Baena, Daniele Dini

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Abstract

Although convection-enhanced delivery (CED) can successfully facilitate a bypass of the blood brain barrier, its treatment efficacy remains highly limited in clinic. This can be partially attributed to the brain anisotropic characteristics that lead to the difficulties in controlling the drug spatial distribution. Here, the responses of six different drugs to the tissue anisotropy are examined through a parametric study performed using a multiphysics model, which considers interstitial fluid flow, tissue deformation and interlinked drug transport processes in CED. The delivery outcomes are evaluated in terms of the penetration depth and delivery volume for effective therapy. Simulation results demonstrate that the effective penetration depth in a given direction can be improved with the increase of the corresponding component of anisotropic characteristics. The anisotropic tissue permeability could only reshape the drug distribution in space but has limited contribution to the total effective delivery volume. On the other hand, drugs respond in different ways to the anisotropic diffusivity. The large delivery volumes of fluorouracil, carmustine, cisplatin and doxorubicin could be achieved in relatively isotropic tissue, while paclitaxel and methotrexate are able to cover enlarged regions into anisotropic tissues. Results obtained from this study serve as a guide for the design of CED treatments.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
JournalDrug Delivery
Volume26
Issue number1
Early online date30 Jul 2019
DOIs
Publication statusPublished - 2019

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Convection
Anisotropy
Permeability
Pharmaceutical Preparations
Carmustine
Extracellular Fluid
Paclitaxel
Blood-Brain Barrier
Methotrexate
Fluorouracil
Doxorubicin
Cisplatin
Brain

Keywords

  • anisotropy
  • convection-enhanced delivery
  • drug transport
  • mathematical body

Cite this

Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery. / Zhan, Wenbo (Corresponding Author); Baena, Ferdinando Rodriguez y; Dini, Daniele.

In: Drug Delivery, Vol. 26, No. 1, 2019, p. 773-781.

Research output: Contribution to journalArticle

Zhan, Wenbo ; Baena, Ferdinando Rodriguez y ; Dini, Daniele. / Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery. In: Drug Delivery. 2019 ; Vol. 26, No. 1. pp. 773-781.
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