Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93040, Regensburg, Germany.
Adv Healthc Mater. 2018 Feb;7(3). doi: 10.1002/adhm.201700739. Epub 2017 Nov 9.
Although nanosized drug delivery systems are promising tools for the treatment of severe diseases, the extracellular matrix (ECM) constitutes a major obstacle that endangers therapeutic success. Mobility of diffusing species is restricted not only by small pore size (down to as low as 3 nm) but also by electrostatic interactions with the network. This article evaluates commonly used in vitro models of ECM, analytical methods, and particle types with respect to their similarity to native conditions in the target tissue. In this cross-study evaluation, results from a wide variety of mobility studies are analyzed to discern general principles of particle-ECM interactions. For instance, cross-linked networks and a negative network charge are essential to reliably recapitulate key features of the native ECM. Commonly used ECM mimics comprised of one or two components can lead to mobility calculations which have low fidelity to in vivo results. In addition, analytical methods must be tailored to the properties of both the matrix and the diffusing species to deliver accurate results. Finally, nanoparticles must be sufficiently small to penetrate the matrix pores (ideally R < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (R >> 1) or positively charged particles are trapped.
尽管纳米药物递送系统是治疗严重疾病的有前途的工具，但细胞外基质 (ECM) 构成了危及治疗成功的主要障碍。扩散物质的迁移不仅受到小孔径（低至 3nm）的限制，还受到与网络的静电相互作用的限制。本文评估了 ECM 的常用体外模型、分析方法和颗粒类型，以了解它们与靶组织中天然条件的相似性。在这项交叉研究评估中，分析了来自各种迁移率研究的结果，以辨别颗粒-ECM 相互作用的一般原理。例如，交联网络和负网络电荷对于可靠地再现天然 ECM 的关键特征至关重要。由一种或两种成分组成的常用 ECM 模拟物可导致与体内结果的迁移率计算具有低保真度。此外，分析方法必须针对基质和扩散物质的特性进行调整，以提供准确的结果。最后，纳米颗粒必须足够小才能穿透基质孔（理想情况下 R < 0.5；d = 颗粒直径，p = 孔径）并带有中性表面电荷以避免阻塞。较大的（R >> 1）或带正电荷的颗粒会被捕获。
