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

Rosa D'Apolito, Giovanna Tomaiuolo*, Francesca Taraballi, Silvia Minardi, Dickson Kirui, Xuewu Liu, Armando Cevenini, Roberto Palomba, Mauro Ferrari, Francesco Salvatore, Ennio Tasciotti, Stefano Guido

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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 vesselwall. 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 showthat 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.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalJournal of Controlled Release
Volume217
DOIs
StatePublished - Nov 10 2015

Keywords

  • Drug delivery
  • Margination
  • Micro-particles
  • Microcirculation
  • Red blood cells
  • Shape
  • Size

ASJC Scopus subject areas

  • Pharmaceutical Science

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