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摘要
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To be one of effective delivery of anticancer therapeutic agents must rely on macromolecular drug carriers because they appear to target tumors and have limited toxicity in normal tissue. However, solid tumors consist of extreme complicated structures: a porous interstitium and a poorly organized vasculature composed of a network of capillaries with highly permeable walls. As anticancer drugs distribute within tumors, they form gradients from tumour blood vessels that change with time as the drug is cleared from the body. The purpose of this study is to better understand macromolecular drug transport mechanisms within solid tumors by numerical calculation. With integrating experimental information on dextran covalently linked to a fluorophore in tumors, optimization scheme, mathematical modeling and numerical modeling, an estimation scheme is proposed to predict several parameters of interest in tumour region. In the study a one-dimensional transient solute transport equation coupled with experimental pharmacokinetics data is used. The governing equation, which is derived from cylindrical coordinates, includes convection and diffusion modes of transport. Applying both an optimization scheme and water-fall searching approach in the study, we predicted macromolecular diffusivities and shifting velocities in tumour region. The results show in a good agreement with experimental data. |
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