(601at) Imaging Distribution Profile of Spherical Drug Carriers in Physiological Blood Flow Conditions

Introduction: Drug delivery systems are vital for reducing adverse effects while maximizing effectiveness.  A novel approach currently being researched involves drug carrying particles delivering the dose to targeted areas. While there is strong evidence that particles can achieve this, a major setback has been the inability for particles to leave the bulk flow of the blood stream and localize to endothelial cells where the drug can internalize and reach the damaged tissues. It has been shown that particle size is an important factor in the margination process (localization and adhesion to the endothelial wall). Nevertheless, there is little experimental evidence to understand how particles behave in the red blood cell (RBC) bulk flow. In our work, we study the ability of spherical drug carriers to transport throughout the vascular blood flow and marginate to endothelial cells by particle distribution profile throughout laminar blood stream. We evaluate the effect of hematocrit on the ability for different sized particles as well as different shear rate conditions.

Method: We investigated the distribution profile of polystyrene spherical particles (500 nm and 2 µm in diameter) in flow chambers (100 µm height) by confocal microscopy. Particles were captured by speed camera in vertical stacks every 5 µm height throughout chambers during blood flow. The human washed blood was fixed at 10, 20 and 30% hematocrit in phosphate buffer and flowed under 100s^-1 and 200s^-1 shear rates. The pictures were then analyzed to determine the amount of particles found in the vertical slice.

Results: It was discovered that when both sized particles are run in phosphate buffer, a normal distribution occurs resulting in the majority of the particles found in the middle of flow. After introducing washed blood into the system, 2 µm polystyrene spheres spread to the wall of the chamber at a higher rate than 500 nm spheres when increasing levels of hematocrit. The distribution of 500 nm spheres becomes bimodal; however, the near wall particles still do not increase in quantity. The results suggest that 2 µm particles interact with RBCs, pushing particles into plasma cell free layer (CFL). Additionally, the dispersion is higher when hematocrit is increased. Conversely, 500 nm particles were trapped in RBCs bulk flow, not near wall particles. 

Conclusion: This work demonstrated the distribution profile of spherical drug carriers in a blood flow system can be significantly influenced by factors which include: particle size, shear rate, vascular size and hematocrit. These factors, therefore, should be considered when designing drug carriers to increase efficiency of delivery systems.