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Mathematical Modelling of Convection Enhanced Delivery of Carmustine and Paclitaxel for Brain Tumour Therapy

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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.

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Abbreviations

BBB:

Blood–brain Barrier

CED:

Convection enhanced delivery

CM:

Cell Membrane

ECS:

Extracellular Space

ICS:

Intracellular Space

IFP:

Interstitial Fluid Pressure

IFV:

Interstitial Fluid Velocity

MRI:

Magnetic Resonance Image

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ACKNOWLEDGMENTS AND DISCLOSURES

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.

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Authors and Affiliations

  1. NUS Environmental Research Institute, National University of Singapore, 1 Create Way, Create Tower #15-02, Singapore, Singapore, 138602

    Wenbo Zhan

  2. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, Singapore, 117585

    Davis Yohanes Arifin & Chi-Hwa Wang

  3. The Brain & Spine Clinic, Gleneagles Hospital, Annex Block #03-38, Singapore, Singapore, 258500

    Timothy KY Lee

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  1. Wenbo Zhan
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Correspondence to Chi-Hwa Wang.

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Zhan, W., Arifin, D.Y., Lee, T.K. et al. Mathematical Modelling of Convection Enhanced Delivery of Carmustine and Paclitaxel for Brain Tumour Therapy. Pharm Res 34, 860–873 (2017). https://doi.org/10.1007/s11095-017-2114-6

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  • DOI: https://doi.org/10.1007/s11095-017-2114-6

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