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首页> 外文期刊>Pharmaceutical Research >Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?
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Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

机译：微粒系统的血管内递送：几何确实重要吗？

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摘要

In cancer therapy and imaging, the systemic passive delivery of particulate systems has relied on the enhanced permeability and retention (EPR) effect: sufficiently small particles can cross the endothelial fenestrations and accumulate in the tumor parenchyma. The vast majority of man-made particulates exhibit a spherical shape as a result of surface energy minimization during their synthesis. The advent of phage display libraries, which are revealing the extraordinary molecular diversity of endothelial cells, and the development of processes for fabricating particles with shapes other than spherical are opening the path to new design solutions for systemically administered targeted particulates. In this paper, the role of particle geometry (i.e., size and shape) is discussed at the tissue and cellular scales. Emphasis is placed on how the synergistic effect of particle geometry and molecular targeting can enhance the specificity of delivery. The intravascular delivery process has been broken into three events: margination, firm adhesion and control of internalization. Predictions from mathematical models and observations from in-vitro experiments were used to show the relevance of particle geometry in systemic delivery. Rational design of particulate systems should consider, beside the physico-chemical properties of the surface coatings, geometrical features as size and shape. The integration of mathematical modeling with in-vitro and in-vivo testing provides the tools for establishing a rational design of nanoparticles.
机译：在癌症治疗和影像学中，微粒系统的全身被动传递依赖于增强的渗透性和保留（EPR）效果：足够小的微粒可以穿过内皮窗并积聚在肿瘤实质中。由于合成过程中表面能的最小化，绝大多数人造颗粒均呈球形。噬菌体展示文库的出现揭示了内皮细胞非凡的分子多样性，制造球形以外的形状的颗粒的方法的发展为系统地施用目标颗粒的新设计解决方案开辟了道路。在本文中，在组织和细胞尺度上讨论了粒子几何形状（即大小和形状）的作用。重点放在颗粒几何形状和分子靶向的协同作用如何增强递送的特异性上。血管内递送过程已分为三个事件：切缘，牢固粘附和控制内在化。数学模型的预测结果和体外实验的观察结果均被用来表明粒子几何形状在全身给药中的相关性。除表面涂层的物理化学性质外，颗粒体系的合理设计还应考虑几何特征（如大小和形状）。数学建模与体外和体内测试的集成为建立合理的纳米颗粒设计提供了工具。

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