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

JOURNAL OF CONTROLLED RELEASE

卷:217

Article

D'Apolito, Rosa^1,4  Tomaiuolo, Giovanna^1,4  Taraballi, Francesca²  Minardi, Silvia²  Kirui, Dickson^2,5  Liu, Xuewu²  Cevenini, Armando³  Palomba, Roberto^2,4  Ferrari, Mauro²  Salvatore, Francesco^3,4  Tasciotti, Ennio²  Guido, Stefano^1,4 

[1] Univ Naples Federico II, Dipartimento Ingn Chim Mat & Prod Ind, Naples, Italy

[2] Houston Methodist Res Inst, Dept NanoMed, Houston, TX USA

[3] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy

[4] CEINGE Biotecnol Avanzate, Naples, Italy

[5] Naval Med Res Unit, San Antonio, TX USA

关键词: Margination;    Microcirculation;    Red blood cells;    Drug delivery;    Micro-particles;    Size;    Shape;   

DOI  :  10.1016/j.jconrel.2015.09.013

来源: Elsevier

【 摘 要 】

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. (c) 2015 Elsevier B.V. All rights reserved.

【 授权许可】

Free