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.
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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).
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Associate Editor Umberto Morbiducci oversaw the review of this article.
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Piergiovanni, M., Casagrande, G., Taverna, F. et al. Shear-Induced Encapsulation into Red Blood Cells: A New Microfluidic Approach to Drug Delivery. Ann Biomed Eng 48, 236–246 (2020). https://doi.org/10.1007/s10439-019-02342-w
- Micro-particle image velocimetry
- Computational fluid dynamic
- Two-phase mixture model
- Drug carrier