Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

By P. Decuzzi, R. Pasqualini, W. Arap, Mauro Ferrari. Pharmaceutical Research, 2008

603 citations recorded by the source corpus.

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.

Subfields: Biomaterials, Electronic, Optical and Magnetic Materials, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/892824e8db1fc15216e46ebe030c51a213f514f2

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Citations in the corpus

Physical approaches to biomaterial design (2009, background): “Theoretical models have already pointed to the benefits of using non-spherical particles for drug delivery based on their influence on cellular internalization and vascular dynamic”
Tuning the Magnetic Properties of Nanoparticles (2013, background): “While the correlation between magnetization and shape is not as direct, the effect of geometry on magnetic properties continues to be evaluated for biosensing applications [16,17].”
Sol-gel based materials for biomedical applications (2016, background): “This property of resorption allows for a variety of new biomedical applications, such as temporary implants that can be replaced with natural tissue as the body repairs a wound or DDSs that allow local and sustained release of macromolecules at the implant site [104,106].”
Delivering nanomedicine to solid tumors (2010, background): “For spherical particles, it has been shown that internalization is faster for smaller particles and might follow a different mechanism than for larger particles”
Techniques for physicochemical characterization of nanomaterials (2013, background): “In addition to size and surface properties, the shape of nanomaterial can play an important role in drug delivery, degradation, transport, targeting and internalization (Champion et al., 2007; Decuzzi et al., 2009; Euliss et al., 2006; Geng et al., 2007; Gratton et al., 2008; Jiang et al., 2013; Mit”