Abstract
Purpose
Convection enhanced delivery (CED) is a promising method of anticancer treatment to bypass the blood–brain barrier. This paper is aimed to study drug transport under different CED operating conditions.
Methods
The convection enhanced delivery of chemotherapeutics to an intact and a remnant brain tumour after resection is investigated by means of mathematical modelling of the key physical and physiological processes of drug transport. Realistic models of brain tumour and its holding tissue are reconstructed from magnetic resonance images. Mathematical modelling is performed for the delivery of carmustine and paclitaxel with different infusion rates, solution concentrations and locations of infusion site.
Results
Modelling predications show that drug penetration can be improved by raising the infusion rate and the infusion solution concentration. The delivery of carmustine with CED is highly localised. High drug concentration only can be achieved around the infusion site. The transport of paclitaxel is more sensitive to CED-enhanced interstitial fluid as compared to carmustine, with deeper penetration into tumour interior. Infusing paclitaxel in the upstream of interstitial fluid flow leads to high spatial averaged concentration and relatively uniform distribution.
Conclusion
Results obtained in this study can be used to guide the design and optimisation of CED treatment regimens.
Convection enhanced delivery (CED) is a promising method of anticancer treatment to bypass the blood–brain barrier. This paper is aimed to study drug transport under different CED operating conditions.
Methods
The convection enhanced delivery of chemotherapeutics to an intact and a remnant brain tumour after resection is investigated by means of mathematical modelling of the key physical and physiological processes of drug transport. Realistic models of brain tumour and its holding tissue are reconstructed from magnetic resonance images. Mathematical modelling is performed for the delivery of carmustine and paclitaxel with different infusion rates, solution concentrations and locations of infusion site.
Results
Modelling predications show that drug penetration can be improved by raising the infusion rate and the infusion solution concentration. The delivery of carmustine with CED is highly localised. High drug concentration only can be achieved around the infusion site. The transport of paclitaxel is more sensitive to CED-enhanced interstitial fluid as compared to carmustine, with deeper penetration into tumour interior. Infusing paclitaxel in the upstream of interstitial fluid flow leads to high spatial averaged concentration and relatively uniform distribution.
Conclusion
Results obtained in this study can be used to guide the design and optimisation of CED treatment regimens.
| Original language | English |
|---|---|
| Pages (from-to) | 860-873 |
| Number of pages | 14 |
| Journal | Pharmaceutical Research |
| Volume | 34 |
| DOIs | |
| Publication status | Published - 2 Feb 2017 |
Bibliographical note
The authors acknowledge the funding support from the National Medical Research Council (NMRC, Singapore) under the grant numbers NMRC EDG11may084, and support from the National Research Foundation, Prime Minister’s Office, Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) programme. Grant Number R-706-001-101-281, National University of Singapore. The authors thank the Supercomputing and Visualization Unit (SVU) of National University of Singapore for providing facilities to perform all the simulation works in this project, and Wei-Cheng Yan for his support in literature review.Keywords
- anticancer therapy
- brain tumour
- convection enhanced delivery
- drug transport
- mathematical model
