Glycoprotein VI (GPVI) functionalized drug carriers for targeted drug delivery at atherothrombotic sites

Atherothrombosis is the major cause of acute coronary syndromes (ACS) and cardiovascular related death. The ability to target drugs specifically to atherothrombotic sites, may be beneficial in reducing side effects as well as increasing the efficacy of drugs that can inhibit atherothrombosis progression. The platelet-specific collagen receptor (GPVI) might be a suitable molecule that can be leveraged to functionalize nanoparticle drug carriers for selective targeting to atherothrombotic sites.

Hemodynamics play a central role in cardiovascular targeted drug delivery systems. Sites of abnormal vascular narrowing (stenosis) exhibit unique flow features including an abnormally elevated level of shear stress as well re-circulating flows downstream of the narrowing.

Here we study the deposition of particulate drug carries in models of arterial stenosis under defined hemodynamic conditions.

First, fluorescently tagged Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles functionalized with GPVI have been fabricated. Then experiments in a microfluidic channels coated with collagen were performed to characterize the adhesion properties of the examined particles as a function of shear. Next, perfusion experiments on collagen coated millimeter sized vascular models of stenotic coronary arteries have been performed using a custom-built perfusion system capable of emulating pulsatile physiological flow. The particle deposition was monitored using time-lapse fluorescence microscopy at defined locations within the model. Our results show that particle size, GPVI coating density and shear affect the deposition pattern within the stenosis and that there is correlation between the microfluidic results under defined shear stress and the deposition in the stenosis models.