Prokop Ales, Davidson Jeffrey M
Department of Chemical Engineering, 24th Avenue & Garland Avenues, 107 Olin Hall, Vanderbilt University, Nashville, Tennessee 37235, USA.
J Pharm Sci. 2008 Sep;97(9):3518-90. doi: 10.1002/jps.21270.
This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood-brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list "elementary" phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach.
本文概述了通过纳米载体（NV）进行细胞内药物和基因运输、积累及滞留（统称为药物递送）相关的原理和障碍。目的是将货物递送至特定的细胞内位点，若可能的话，发挥局部作用。本文讨论的一些原理适用于不能透过质膜或血脑屏障的非胶体药物。NV被定义为一系列纳米级颗粒，可形成能够进入细胞和组织并在细胞内递送货物的胶体物质。文中讨论了不同的定位和靶向方法。还对药代动力学和药效学进行了有限的讨论。将NV与微递送及已投入商业使用的当前纳米技术进行了对比。概述了NV技术的最新进展，并强调了其未来应用。我们还简要回顾了现有的建模工具和方法，以定量描述靶向NV在血管和肿瘤区室中的行为，这是一个特别重要的领域。在列出与癌症递送不同复杂程度相关的“基本”现象时，我们也强调了多尺度建模和自下而上的系统生物学方法的重要性。
