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A Mathematical Model for Thermosensitive Liposomal Delivery of Doxorubicin to Solid Tumour

机译:阿霉素对实体瘤热敏脂质体递送的数学模型

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摘要

The effectiveness of anticancer treatments is often hampered by the serious side effects owing to toxicity of anticancer drugs and their undesirable uptake by healthy cells in vivo. Thermosensitive liposome-mediated drug delivery has been developed as part of research efforts aimed at improving therapeutic efficacy while reducing the associated side effect. Since multiple steps are involved in the transport of drug-loaded liposomes, drug release, and its uptake, mathematical models become an indispensible tool to analyse the transport processes and predict the outcome of anticancer treatment. In this study, a computational model is developed which incorporates the key physical and biochemical processes involved in drug delivery and cellular uptake. The model has been applied to idealized tumour geometry, and comparisons are made between continuous infusion of doxorubicin and thermosensitive liposome-mediated delivery. Results show that thermosensitive liposome-mediated delivery performs better in reducing drug concentration in normal tissues, which may help lower the risk of associated side effects. Compared with direct infusion over a 2-hour period, thermosensitive liposome delivery leads to a much higher peak intracellular concentration of doxorubicin, which may increase cell killing in tumour thereby enhancing the therapeutic effect of the drug.
机译:由于抗癌药的毒性以及健康细胞在体内对它们的不良吸收,抗癌治疗的有效性常常受到严重副作用的困扰。热敏脂质体介导的药物递送已经被开发为旨在改善治疗功效同时减少相关副作用的研究工作的一部分。由于载药脂质体的运输,药物释放及其吸收涉及多个步骤,因此数学模型成为分析运输过程和预测抗癌治疗结果必不可少的工具。在这项研究中,开发了一种计算模型,其中包含了与药物递送和细胞摄取有关的关键物理和生化过程。该模型已应用于理想的肿瘤几何结构,并在连续输注阿霉素和热敏脂质体介导的递送之间进行了比较。结果表明,热敏脂质体介导的递送在降低正常组织中的药物浓度方面表现更好,这可能有助于降低相关副作用的风险。与2小时内的直接输注相比,热敏脂质体的输送导致阿霉素峰值细胞内浓度高得多,这可能会增加肿瘤细胞的杀伤力,从而增强药物的治疗效果。

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