A Mathematical Model for the Transport of Paclitaxel (Taxol) Across the Blood-Brain Barrier

Paclitaxel (Taxol) from Taxus brevifolia is an antimitotic drug that is successfully used in the fight against many different types of cancers. However, exclusion of paclitaxel from the central nervous system by the blood-brain barrier is a major obstacle for paclitaxel-based treatment of glioma. Here, we propose a mathematical model for the transport of paclitaxel across the blood-brain barrier, based on ordinary differential equations, which considers (1) passive diffusion across the luminal and the abluminal membrane of brain capillaries, (2) luminal blood-binding and binding to microtubules within the brain capillary endothelial cells, and (3) active transport of paclitaxel from the endothelial cells to the vascular lumen by p-glycoprotein. With experimental data published previously, we show that the parameters of this model can be estimated with a simple experimental setup. The model presented here might support the rational development of targeting strategies in silico for efficiently delivering drugs across the blood-brain barrier.

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