PDF(Pubmed)
Abstract：
Focused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach. Equations are then solved by finite element methods to calculate intracellular drug concentration and treatment efficacy. The main objective of this study is to present a multi-physics and multi-scale model to simulate drug release, transport, and delivery to solid tumors, followed by an analysis of how FUS exposure time and drug release rate affect these processes. Our findings not only show the capability of model to replicate this therapeutic approach, but also confirm the benefits of this treatment with an improvement of drug aggregation in tumor and reduction of drug delivery in healthy tissue. For instance, the survival fraction of tumor cells after this treatment dropped to 62.4%, because of a large amount of delivered drugs to cancer cells. Next, a combination of three release rates (ultrafast, fast, and slow) and FUS exposure times (10, 30, and 60 min) was examined. Area under curve (AUC) results show that the combination of 30 min FUS exposure and rapid drug release leads to a practical and effective therapeutic response.
摘要：
聚焦超声（FUS）触发的纳米级药物输送，作为治疗实体瘤的智能刺激响应系统，进行了计算研究，以增强药物的局部递送和治疗功效。热敏脂质体（TSL）的整合，作为负载多柔比星（DOX）的纳米载体，FUS,提供了一种有前途的药物递送系统。完全耦合的偏微分方程组，包括FUS传播的Helmholtz方程，生物传热，间质液流量,药物在组织和细胞空间的运输，首先提出了这种治疗方法的药效学模型。然后通过有限元方法求解方程以计算细胞内药物浓度和治疗功效。这项研究的主要目的是提出一个多物理和多尺度模型来模拟药物释放，运输,并运送到实体瘤，然后分析FUS暴露时间和药物释放速率如何影响这些过程。我们的发现不仅显示了模型复制这种治疗方法的能力，但也证实了这种治疗的好处，改善了肿瘤中的药物聚集和减少了健康组织中的药物递送。例如,治疗后肿瘤细胞的存活率下降到62.4%，因为大量的药物被输送到癌细胞。接下来,三种释放速率的组合(超快，快,和缓慢）和FUS暴露时间（10、30和60分钟）进行检查。曲线下面积(AUC)结果表明,30分钟FUS暴露和快速药物释放的组合导致实际和有效的治疗反应。
