In vitro microfluidic platform for cardiovascular targeted drug carrier design

Vascular-targeted carriers (VTCs) carry great potential for treatment of cardiovascular diseases by providing exact transport of therapeutic factors to a specific target site. However, despite decades of research, the dynamic interactions that control the transport of these particles in blood are still not fully understood, and unfortunately until now VTCs based systems had shown poor clinical efficacy.¹ A major requirement for efficient VTC system is that all particulate carriers effectively localize to the vascular wall upon injection into the bloodstream. In their way to the vessel wall VTCs must overcome collisions with the various blood components, and avoid interaction with the immune system cells. Particles properties such as shape, size and stiffness affect their motion and trajectory in blood as well as their interactions with the different blood components.^1.2 For successful drug delivery, it is crucial to find particles that effectively localize to the vascular wall without the high risk of vessel occlusion in the capillaries. Here, we propose to leverage advanced microfluidic in vitro platforms of pulmonary capillary networks to evaluate the ability of various particles to navigate the vast capillary bed without occlusion. Our microfluidic model allows in vitro study of human RBC flow in capillaries at true scale.³ In addition, several parameter spaces can be rapidly explored to optimize the performance of the proposed particles in blood stream while avoiding costly in vivo experiments.

References:

1) Gupta, A. Sen. Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature. WIREs Nanomed Nanobiotechnol 8, 255–270 (2016).

2) Charoenphol, P., Onyskiw, P. J., Carrasco-Teja, M. & Eniola-Adefeso, O. Particle-cell dynamics in human blood flow: Implications for vascular-targeted drug delivery. J. Biomech. 45, 2822–2828 (2012)

3) Stauber, H., Waisman, D., Korin, N. & Sznitman, J. Red blood cell dynamics in biomimetic microfluidic networks of pulmonary alveolar capillaries. Biomicrofluidics, 11(1),014103 (2017)