Kirtane Ameya R, Siegel Ronald A, Panyam Jayanth
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55455.
J Pharm Sci. 2015 Mar;104(3):1174-86. doi: 10.1002/jps.24302. Epub 2015 Jan 12.
Drug carriers in the ∼ 100 nm size range are of considerable interest in the field of cancer therapy because of their ability to passively accumulate in tumors. Tailoring the physicochemical properties of these carriers to individual patient requirements will help exploit their full therapeutic potential. Here, we present a pharmacokinetic model to explain how vascular physiology could be used to guide the optimal choice of specific formulation parameters. We find that in order to maximize the benefit-to-risk ratio, nanosystems should be confined to a specific particle size range. The optimal particle size range is dictated by the vascular pore size of not only the tumor tissue but also of the normal organs. Additionally, the duration of drug release is a key variable that can be used to maximize the therapeutic benefit of nanomedicine. Our model further suggests that the enhanced permeability and retention effect is not necessarily a universal outcome for every nanocarrier in every tumor model but will only be observed for nanoparticles of a specific size range. This optimal size range, in turn, is governed by the vascular physiology of the tumor and of non-target organs.
尺寸在100纳米左右的药物载体在癌症治疗领域备受关注，因为它们能够被动地在肿瘤中蓄积。根据个体患者的需求调整这些载体的物理化学性质，将有助于充分发挥其治疗潜力。在此，我们提出一种药代动力学模型，以解释如何利用血管生理学来指导特定制剂参数的最佳选择。我们发现，为了使风险效益比最大化，纳米系统应限定在特定的粒径范围内。最佳粒径范围不仅取决于肿瘤组织的血管孔径，还取决于正常器官的血管孔径。此外，药物释放的持续时间是一个关键变量，可用于使纳米药物的治疗效益最大化。我们的模型进一步表明，增强的渗透与滞留效应并不一定是每个肿瘤模型中每种纳米载体的普遍结果，而仅在特定粒径范围内的纳米颗粒中才会观察到。反过来，这个最佳粒径范围又受肿瘤和非靶器官的血管生理学支配。
