Convection enhanced delivery of chemotherapeutic drugs into brain tumour


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Abstract

Convection enhanced delivery (CED) of chemotherapeutic drugs can successfully bypass the blood-brain barrier (BBB). However, the treatment efficacy is significantly variable in clinic owing to the absence of proper drugs and the lack of understanding on the local drug transport. In this study, mathematical modelling is employed to investigate the suitability of six chemotherapeutic drugs from the perspective of intratumoural transport, including fluorouracil, carmustine, cisplatin, methotrexate, doxorubicin and paclitaxel. The convection/diffusion/reaction model coupled with Darcy's law is applied to a 3-D realistic brain tumour model that is extracted from magnetic resonance (MR) images. The modelling demonstrates the advantages of CED in enhancing the convective flow of interstitial fluid and reducing the drug concentration dilution caused by the fluid loss from blood stream in the tumour region around the infusion site. The delivery outcomes of the drug in CED treatments are strongly dependent on its physicochemical properties. Convection is more effective in determining the transport of paclitaxel and methotrexate in brain tumour. Paclitaxel exhibits its superiority in drug penetration and accumulation, resulting in the largest effective delivery volume as compared to the other studied drugs. Nanocarrier and diagnostic ultrasound are able to enhance the drug penetration for achieving improved delivery outcomes. Results obtained in this study can serve as a guide for optimising CED treatment regimens.Graphic abstractThe delivery outcomes of six figure-mentioned anticancer drugs upon convection-enhanced delivery are studied based on a multiphasical model. Paclitaxel shows the superiority for chemotherapy as compared to the other drugs.

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