Zhan Wenbo, Gedroyc Wladyslaw, Xu Xiao Yun
Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ.
Protein Pept Lett. 2014;21(11):1146-56. doi: 10.2174/0929866521666140807115629.
Effective delivery of therapeutic agents to tumour cells is essential to the success of most cancer treatment therapies except for surgery. The transport of drug in solid tumours involves multiple biophysical and biochemical proc- esses which are strongly dependent on the physicochemical properties of the drug and biological properties of the tumour. Owing to the complexities involved, mathematical models are playing an increasingly important role in identifying the factors leading to inadequate drug delivery to tumours. In this study, a computational model is developed which incorpo- rates real tumour geometry reconstructed from magnetic resonance images, drug transport through the tumour vasculature and interstitium, as well as drug uptake by tumour cells. The effectiveness of anticancer therapy is evaluated based on the percentage of survival tumour cells by directly solving the pharmacodynamics equation using predicted intracellular drug concentrations. Computational simulations are performed for the delivery of doxorubicin through different administration modes and doses. Our predictions show that continuous infusion is far more effective than bolus injection in maintaining high levels of intracellular drug concentration, thereby increasing drug uptake by tumour cells. On the other hand, bolus injection leads to higher extracellular concentration in both tumour and normal tissues compared to continuous infusion, which is undesirable as high drug concentration in normal tissues may increase the risk of associated side effects.
除手术外，将治疗药物有效递送至肿瘤细胞对大多数癌症治疗方法的成功至关重要。实体瘤中药物的转运涉及多个生物物理和生化过程，这些过程强烈依赖于药物的物理化学性质和肿瘤的生物学特性。由于涉及的复杂性，数学模型在确定导致药物向肿瘤递送不足的因素方面发挥着越来越重要的作用。在本研究中，开发了一种计算模型，该模型整合了从磁共振图像重建的真实肿瘤几何形状、药物通过肿瘤血管系统和间质的转运以及肿瘤细胞对药物的摄取。通过使用预测的细胞内药物浓度直接求解药效学方程，基于存活肿瘤细胞的百分比评估抗癌治疗的有效性。针对通过不同给药方式和剂量递送阿霉素进行了计算模拟。我们的预测表明，持续输注在维持高水平的细胞内药物浓度方面远比推注有效，从而增加肿瘤细胞对药物的摄取。另一方面，与持续输注相比，推注在肿瘤组织和正常组织中均导致更高的细胞外浓度，这是不理想的，因为正常组织中的高药物浓度可能增加相关副作用的风险。
