Effect of tissue permeability and drug diffusion anisotropy on convection-enhanced delivery
File(s)WZhan_DrugDelivery_2019.pdf (1.49 MB)
Published version
Author(s)
Zhan, Wenbo
Rodriguez y Baena, Ferdinando
Dini, Daniele
Type
Journal Article
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.
Date Issued
2019-07-30
Date Acceptance
2019-07-01
Citation
Drug Delivery, 2019, 26 (1), pp.773-781
ISSN
1071-7544
Publisher
Taylor & Francis Open
Start Page
773
End Page
781
Journal / Book Title
Drug Delivery
Volume
26
Issue
1
Copyright Statement
© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Commission of the European Communities
Identifier
https://www.tandfonline.com/doi/full/10.1080/10717544.2019.1639844
Grant Number
688279
Subjects
1115 Pharmacology and Pharmaceutical Sciences
Pharmacology & Pharmacy
Publication Status
Published online
Date Publish Online
2019-07-30