Red blood cells affect the margination of microparticles in synthetic microcapillaries and intravital microcirculation as a function of their size and shape

A key step in particle-based drug delivery through microcirculation is particle migration from blood flow to vessel walls, also known as “margination”, which promotes particle contact and adhesion to the vessel wall. Margination and adhesion should be independently addressed as two distinct phenomen...

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Bibliographic Details
Published in:Journal of controlled release 2015-11, Vol.217, p.263-272
Main Authors: D'Apolito, Rosa, Tomaiuolo, Giovanna, Taraballi, Francesca, Minardi, Silvia, Kirui, Dickson, Liu, Xuewu, Cevenini, Armando, Palomba, Roberto, Ferrari, Mauro, Salvatore, Francesco, Tasciotti, Ennio, Guido, Stefano
Format: Article
Language:English
Subjects:
Animals
Capillaries - physiology
Drug delivery
Erythrocytes - physiology
Humans
Lactic Acid - chemistry
Margination
Mice, Transgenic
Micro-particles
Microcirculation
Microfluidics
Microscopy, Confocal
Particle Size
Polyglycolic Acid - chemistry
Red blood cells
Shape
Size
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Summary:A key step in particle-based drug delivery through microcirculation is particle migration from blood flow to vessel walls, also known as “margination”, which promotes particle contact and adhesion to the vessel wall. Margination and adhesion should be independently addressed as two distinct phenomena, considering that the former is a fundamental prerequisite to achieve particle adhesion and subsequent extravasation. Although margination has been modeled by numerical simulations and investigated in model systems in vitro, experimental studies including red blood cells (RBCs) are lacking. Here, we evaluate the effect of RBCs on margination through microfluidic studies in vitro and by intravital microscopy in vivo. We show that margination, which is almost absent when particles are suspended in a cell-free medium, is drastically enhanced by RBCs. This effect is size- and shape-dependent, larger spherical/discoid particles being more effectively marginated both in vitro and in vivo. Our findings can be explained by the collision of particles with RBCs that induces the drifting of the particles towards the vessel walls where they become trapped in the cell-free layer. These results are relevant for the design of drug delivery strategies based on systemically administered carriers. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2015.09.013