Multiscale Kinetic Modeling of Liposomal Doxorubicin Delivery Quantifies the Role of Tumor and Drug-Specific Parameters in Local Delivery to Tumors
Multiscale Kinetic Modeling of Liposomal Doxorubicin Delivery Quantifies the Role of Tumor and Drug-Specific Parameters in Local Delivery to Tumors
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DOI：
10.1038/psp.2012.16
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Wickham, T. J.
中科院分区：
文献类型：
--
作者：
Hendriks, B. S.;Reynolds, J. G.;Wickham, T. J.
纳米颗粒包封已被用作操纵肿瘤学药物的药代动力学（PK）和安全性特征的手段。使用聚乙二醇化脂质体阿霉素（PLD）与传统的阿霉素作为模型系统，我们开发和实验验证了脂质体药物递送的多尺度计算模型。我们证明，对于不同的肿瘤转运特性，存在脂质体和常规多柔比星向肿瘤细胞核递送相同量的多柔比星的方案。在小鼠中，相对于游离药物，典型的肿瘤特性始终有利于通过脂质体改善递送。然而，在人类中，我们预测一些肿瘤将具有这样的性质，其中脂质体递送相对于用游离药物给药将相同量的药物递送至其靶标。鉴定具有高度脂质体沉积的肿瘤类型和/或个体患者肿瘤的能力对于优化纳米颗粒和脂质体抗癌治疗的成功可能是至关重要的。
Nanoparticle encapsulation has been used as a means to manipulate the pharmacokinetic (PK) and safety profile of drugs in oncology. Using pegylated liposomal doxorubicin (PLD) vs. conventional doxorubicin as a model system, we developed and experimentally validated a multiscale computational model of liposomal drug delivery. We demonstrated that, for varying tumor transport properties, there is a regimen where liposomal and conventional doxorubicin deliver identical amounts of doxorubicin to tumor cell nuclei. In mice, typical tumor properties consistently favor improved delivery via liposomes relative to free drug. However, in humans, we predict that some tumors will have properties wherein liposomal delivery delivers the identical amount of drug to its target relative to dosing with free drug. The ability to identify tumor types and/or individual patient tumors with high degree of liposome deposition may be critical for optimizing the success of nanoparticle and liposomal anticancer therapeutics.