Role of tissue hydraulic permeability in convection-enhanced delivery of nanoparticle-encapsulated chemotherapy drugs to brain tumour
File(s)
Published version
Author(s)
Yang, Yi
Zhan, Wenbo
Type
Journal Article
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.
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.
Date Issued
2022-05-01
Date Acceptance
2022-04-07
Citation
Pharmaceutical Research, 2022, 39 (5), pp.877-892
ISSN
0724-8741
Publisher
Springer
Start Page
877
End Page
892
Journal / Book Title
Pharmaceutical Research
Volume
39
Issue
5
Copyright Statement
© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35474156
PII: 10.1007/s11095-022-03261-7
Subjects
brain tumour
CANCER
CEREBROSPINAL-FLUID
Chemistry
Chemistry, Multidisciplinary
convection-enhanced delivery
DOXORUBICIN
drug transport
INTERSTITIAL FLUID
Life Sciences & Biomedicine
mathematical modelling
MICROVASCULAR PERMEABILITY
PHARMACOKINETICS
Pharmacology & Pharmacy
Physical Sciences
Science & Technology
STEALTH LIPOSOMES
TARGETED DELIVERY
TEMOZOLOMIDE
tissue hydraulic permeability
TRANSPORT
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2022-04-26