Optimizing Vascular Drug Delivery Carrier Design using Advanced In Vitro Microvascular Platforms

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. Efficient VTC system requires that particulate carriers effectively marginate toward the vascular wall upon injection into the bloodstream, but also maintain minimum vessel occlusion in the capillaries. Particles properties such as shape, size and stiffness affect their motion and trajectory in blood. Here we develop a tool for testing and screening the navigability of VTCs through a complex network of small capillaries. We use the platform to study the effect of different physical properties of such particles on transport characteristics in small capillaries.

Methods: We leverage advanced microfluidic in vitro platforms utilizing a model of the pulmonary capillary network (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 Understanding the dynamics of carriers in vitro is a crucial step in the design and screening of potential drug carriers. Microfluidics can serve as a good platform for a robust testing of the above parameters at true scale under controlled physiological conditions.