将化疗药物递送至实体瘤对于最佳治疗成功和最小副作用是关键的。我们在数学上开发了一种使用通过光辐射激活的热敏纳米载体的递送方法。评估其疗效并确定影响治疗反应的关键事件和参数,我们将这种方法与单次和多次给药的推注和连续输注阿霉素进行了比较。混合发芽血管生成方法产生半现实的微血管网络,以评估治疗药物的分布和微血管异质性。药效学模型基于肿瘤存活细胞百分比评估治疗成功。研究发现,虽然推注使细胞外药物浓度水平提高了90%,由于改善了生物利用度,连续输注改善了治疗反应.由于长时间的化疗药物暴露,几次注射与单次注射相比,癌细胞死亡增加了6%。然而,在细胞外空间中,响应性纳米载体提供的药物比传统化疗多2.1倍以上,抑制肿瘤发展的时间更长。此外,控制药物释放通过降低循环中游离药物的浓度而显著降低全身副作用。这项工作的主要发现突出了高生物利用度在治疗反应中的重要性。结果表明,响应性纳米载体有助于增加生物利用度,改善治疗效果。通过在半逼真的模型中包含药物输送特征,这项数值研究旨在提高对药物-生物相互作用的理解。该模型为了解临床前和临床靶向肿瘤学研究结果提供了良好的框架。
Delivery of chemotherapeutic medicines to solid tumors is critical for optimal therapeutic success and minimal adverse effects. We mathematically developed a delivery method using thermosensitive nanocarriers activated by light irradiation. To assess its efficacy and identify critical events and parameters affecting therapeutic response, we compared this method to bolus and continuous infusions of doxorubicin for both single and multiple administrations. A hybrid sprouting angiogenesis approach generates a semi-realistic microvascular network to evaluate therapeutic drug distribution and microvascular heterogeneity. A pharmacodynamics model evaluates treatment success based on tumor survival cell percentage. The
study found that whereas bolus injection boosted extracellular drug concentration levels by 90%, continuous infusion improved therapeutic response due to improved bioavailability. Cancer cell death increases by 6% with several injections compared to single injections due to prolonged chemotherapeutic medication exposure. However, responsive nanocarriers supply more than 2.1 times more drug than traditional chemotherapy in extracellular space, suppressing tumor development longer. Also, controlled drug release decreases systemic side effects substantial through diminishing the concentration of free drug in the circulation. The primary finding of this work highlights the significance of high bioavailability in treatment response. The results indicate that responsive nanocarriers contribute to increased bioavailability, leading to improved therapeutic benefits. By including drug delivery features in a semi-realistic model, this numerical
study sought to improve drug-bio interaction comprehension. The model provides a good framework for understanding preclinical and clinical targeted oncology
study outcomes.