Ozturk Deniz, Yonucu Sirin, Yilmaz Defne, Unlu Mehmet Burcin
Department of Physics, Bogazici University, 34342 Bebek, Istanbul, Turkey. Center for Life Sciences and Technologies, Bogazici University, 34342 Bebek, Istanbul, Turkey.
Phys Med Biol. 2015 Feb 21;60(4):1477-96. doi: 10.1088/0031-9155/60/4/1477. Epub 2015 Jan 22.
Elevated interstitial fluid pressure is one of the barriers of drug delivery in solid tumors. Recent studies have shown that normalization of tumor vasculature by anti-angiogenic factors may improve the delivery of conventional cytotoxic drugs, possibly by increasing blood flow, decreasing interstitial fluid pressure, and enhancing the convective transvascular transport of drug molecules. Delivery of large therapeutic agents such as nanoparticles and liposomes might also benefit from normalization therapy since their transport depends primarily on convection. In this study, a mathematical model is presented to provide supporting evidence that normalization therapy may improve the delivery of 100 nm liposomes into solid tumors, by both increasing the total drug extravasation and providing a more homogeneous drug distribution within the tumor. However these beneficial effects largely depend on tumor size and are stronger for tumors within a certain size range. It is shown that this size effect may persist under different microenvironmental conditions and for tumors with irregular margins or heterogeneous blood supply.
间质液压力升高是实体瘤药物递送的障碍之一。最近的研究表明，抗血管生成因子使肿瘤血管正常化可能会改善传统细胞毒性药物的递送，这可能是通过增加血流量、降低间质液压力以及增强药物分子的对流性跨血管转运来实现的。纳米颗粒和脂质体等大型治疗剂的递送也可能从正常化治疗中受益，因为它们的转运主要依赖于对流。在本研究中，提出了一个数学模型，以提供支持性证据，即正常化治疗可能通过增加药物总外渗量并在肿瘤内提供更均匀的药物分布，从而改善100纳米脂质体向实体瘤的递送。然而，这些有益效果在很大程度上取决于肿瘤大小，并且对于一定大小范围内的肿瘤更为明显。结果表明，这种大小效应在不同的微环境条件下以及对于边缘不规则或血液供应不均一的肿瘤可能持续存在。
