An In vitro Microfluidic Pulmonary Capillary Network Model for Optimizing Intravascular Drug Carriers

Introduction: Vascular-targeted carriers (VTCs) carry great potential for treatment of cardiovascular diseases. However, the dynamic interactions that control the transport of these particles in blood are still not fully understood, and thus hider the design of efficient VTCs based systems. A major requirement for efficient VTC system is that particulate carriers effectively marginate toward the vascular wall upon injection into the bloodstream. Particles properties such as shape, size and stiffness affect their motion and trajectory in blood. For successful drug delivery, it is crucial to engineer particles that exhibit both efficient margination as well as minimum vessel occlusion in the capillaries. Here we design and apply a biomimetic microfluidic model of a pulmonary capillary network (PCN) to test the effect of particle properties on vessel occlusion in capillaries.

Methods: We leverage advanced microfluidic in vitro platforms utilizing a model of the PCN to evaluate the ability of various particles to navigate through the vast capillary bed without occlusion. Using this model, several parameters can be rapidly explored to optimize the performance of the particles in blood stream.

Results: Our experiments showed that stiff particles above 3 µm occlude rapidly the system while particles below 2 µm easily passed without entrapment. The occlusion rate of particles between 2-3 µm dramatically depends on the size and concentration.

Conclusions: Optimization of particle parameters is crucial for efficient drug delivery. To achieve efficient margination while maintaining the ability to traverse through small capillaries in vitro microfluidic models can be applied.