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Shear-Induced Encapsulation into Red Blood Cells: A New Microfluidic Approach to Drug Delivery

  • Monica PiergiovanniEmail author
  • Giustina Casagrande
  • Francesca Taverna
  • Ilaria Corridori
  • Marta Frigerio
  • Elena Bianchi
  • Flavio Arienti
  • Arabella Mazzocchi
  • Gabriele Dubini
  • Maria Laura Costantino
Article
  • 84 Downloads

Abstract

Encapsulating molecules into red blood cells (RBCs) is a challenging topic for drug delivery in clinical practice, allowing to prolong the residence time in the body and to avoid toxic residuals. Fluidic shear stress is able to temporary open the membrane pores of RBCs, thus allowing for the diffusion of a drug in solution with the cells. In this paper, both a computational and an experimental approach were used to investigate the mechanism of shear-induced encapsulation in a microchannel. By means of a computational fluid dynamic model of a cell suspension, it was possible to calculate an encapsulation index that accounts for the effective shear acting on the cells, their distribution in the cross section of the microchannel and their velocity. The computational model was then validated with micro-PIV measurements on a RBCs suspension. Finally, experimental tests with a microfluidic channel showed that, by choosing the proper concentration and fluid flow rate, it is possible to successfully encapsulate a test molecule (FITC-Dextran, 40 kDa) into human RBCs. Cytofluorimetric analysis and confocal microscopy were used to assess the RBCs physiological shape preservation and confirm the presence of fluorescent molecules inside the cells.

Keywords

Micro-particle image velocimetry Computational fluid dynamic Two-phase mixture model Erythrocytes Drug carrier Microdevice Micro-hemodynamics 

Notes

Acknowledgments

We thank Dr. Emanuela Iacchetti, Politecnico di Milano, for her essential help in the use of the confocal microscope and Dott. Mariangela Mazzi, Verona University, for helping setup the statistical analysis.

Conflict of interest

M. Piergiovanni, G. Casagrande, E. Bianchi and M.L. Costantino filed a patent based on the results here presented (N. PCT/IB2018/060433—2018, December 21st).

Supplementary material

10439_2019_2342_MOESM1_ESM.docx (474 kb)
Supplementary material 1 (DOCX 473 kb)

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Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  • Monica Piergiovanni
    • 1
    Email author
  • Giustina Casagrande
    • 1
  • Francesca Taverna
    • 2
  • Ilaria Corridori
    • 1
  • Marta Frigerio
    • 1
  • Elena Bianchi
    • 1
  • Flavio Arienti
    • 2
  • Arabella Mazzocchi
    • 2
  • Gabriele Dubini
    • 1
  • Maria Laura Costantino
    • 1
  1. 1.LaBS (Laboratory of Biological Structure mechanics), Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”Politecnico di MilanoMilanItaly
  2. 2.Service of Immunohematology and Transfusion MedicineFondazione IRCCS Istituto Nazionale TumoriMilanItaly

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