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Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-11-09 , DOI: 10.1002/adhm.201700739 Luise Tomasetti 1 , Miriam Breunig 1
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-11-09 , DOI: 10.1002/adhm.201700739 Luise Tomasetti 1 , Miriam Breunig 1
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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 Rd/p < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (Rd/p >> 1) or positively charged particles are trapped.
中文翻译：
通过细胞外基质预防纳米药物递送系统的阻塞
尽管纳米级药物输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。扩散物质的流动性不仅受到小孔径（低至3 nm）的限制，而且还受到与网络的静电相互作用的限制。本文就其与靶组织天然条件的相似性，评估了常用的ECM体外模型，分析方法和颗粒类型。在这项跨研究评估中，分析了各种迁移率研究的结果，以辨别粒子与ECM相互作用的一般原理。例如，交叉链接的网络和负的网络费用对于可靠地概括本机ECM的关键功能至关重要。常用的由一种或两种成分组成的ECM模拟物可能导致迁移率计算，其对体内结果的保真度较低。此外，必须针对基质和扩散物质的特性量身定制分析方法，以提供准确的结果。最后，纳米粒子必须足够小才能穿透基质孔（理想情况下）R d / p <0.5; d =粒径，p =孔径），并带有中性的表面电荷以避免阻塞。较大的（R d / p >> 1）或带正电的粒子被捕获。
更新日期：2017-11-09
中文翻译：
通过细胞外基质预防纳米药物递送系统的阻塞
尽管纳米级药物输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。扩散物质的流动性不仅受到小孔径（低至3 nm）的限制，而且还受到与网络的静电相互作用的限制。本文就其与靶组织天然条件的相似性，评估了常用的ECM体外模型，分析方法和颗粒类型。在这项跨研究评估中，分析了各种迁移率研究的结果，以辨别粒子与ECM相互作用的一般原理。例如，交叉链接的网络和负的网络费用对于可靠地概括本机ECM的关键功能至关重要。常用的由一种或两种成分组成的ECM模拟物可能导致迁移率计算，其对体内结果的保真度较低。此外，必须针对基质和扩散物质的特性量身定制分析方法，以提供准确的结果。最后，纳米粒子必须足够小才能穿透基质孔（理想情况下）R d / p <0.5; d =粒径，p =孔径），并带有中性的表面电荷以避免阻塞。较大的（R d / p >> 1）或带正电的粒子被捕获。
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